| 1. |
|
|
| 2. |
- Librado, P., et al.
(författare)
-
The origins and spread of domestic horses from the Western Eurasian steppes
- 2021
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 634-640
-
Tidskriftsartikel (refereegranskat)abstract
- Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region. Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).
|
|
| 3. |
- Prokunina-Olsson, Ludmila, et al.
(författare)
-
Tissue-specific alternative splicing of TCF7L2
- 2009
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:20, s. 3795-3804
-
Tidskriftsartikel (refereegranskat)abstract
- Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been identified as the strongest genetic risk factors for type 2 diabetes (T2D). However, the mechanisms by which these non-coding variants increase risk for T2D are not well-established. We used 13 expression assays to survey mRNA expression of multiple TCF7L2 splicing forms in up to 380 samples from eight types of human tissue (pancreas, pancreatic islets, colon, liver, monocytes, skeletal muscle, subcutaneous adipose tissue and lymphoblastoid cell lines) and observed a tissue-specific pattern of alternative splicing. We tested whether the expression of TCF7L2 splicing forms was associated with single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, located within introns 3 and 4 of the gene and most strongly associated with T2D. Expression of two splicing forms was lower in pancreatic islets with increasing counts of T2D-associated alleles of the SNPs: a ubiquitous splicing form (P = 0.018 for rs7903146 and P = 0.020 for rs12255372) and a splicing form found in pancreatic islets, pancreas and colon but not in other tissues tested here (P = 0.009 for rs12255372 and P = 0.053 for rs7903146). Expression of this form in glucose-stimulated pancreatic islets correlated with expression of proinsulin (r(2) = 0.84-0.90, P < 0.00063). In summary, we identified a tissue-specific pattern of alternative splicing of TCF7L2. After adjustment for multiple tests, no association between expression of TCF7L2 in eight types of human tissue samples and T2D-associated genetic variants remained significant. Alternative splicing of TCF7L2 in pancreatic islets warrants future studies. GenBank Accession Numbers: FJ010164-FJ010174.
|
|
| 4. |
- Wallin, S., et al.
(författare)
-
Biomonitoring study of deoxynivalenol exposure and association with typical cereal consumption in Swedish adults
- 2013
-
Ingår i: World Mycotoxin Journal. - 1875-0710 .- 1875-0796. ; 6:4, s. 439-448
-
Tidskriftsartikel (refereegranskat)abstract
- Deoxynivalenol (DON) is a mycotoxin of the trichothecene family commonly found in cereals infested with different Fusarium species. DON acts primarily on the gastrointestinal and immune system and is suspected to be an underlying agent causing several outbreaks of gastrointestinal disorder among humans, which prompts studies of human exposure and estimations of intake among populations. However, assessing human exposure to mycotoxins is associated with several difficulties. Therefore, a study was undertaken among adults (18-80 years) in a subgroup of Riksmaten, the Swedish national survey investigating dietary habits, examining both the association between urinary DON concentration and dietary intake of cereals, and estimations of daily DON intake. The results indicate that exposure to DON is common among Swedish adults, as this mycotoxin was detected in 292 out of 326 urine samples (90%) at levels ranging from non-detectable to 65.8 ng DON/mI urine with a median level of 2.9 ng/ml. Furthermore, urinary DON (ng/mg creatinine) was associated with intake (g/day) of total cereal grain as well as whole grain. Urinary DON was also significantly associated with breakfast cereals and porridge consumption (P<0.05). Estimated DON intake in this study ranged between 2.5 and 5,443 ng/kg body weight (bw). 1% of the individuals had estimated intakes above the group provisional maximum tolerable daily intake (PMTDI; 1 mu g/kg), whereas the mean and median intakes of 159 and 84 ng DON/kg bw, respectively, were considerably below the PMTDI. Along with the toxicological profile of DON, no serious health implications are to be expected for the majority of Swedish adults, although a potential health concern remains for some high cereal consumers. In conclusion, biomonitoring could prove to be a valuable tool for observing DON exposure among populations.
|
|
| 5. |
|
|
| 6. |
- Bechta, Sevostian, et al.
(författare)
-
Corium phase equilibria based on MASCA, METCOR and CORPHAD results
- 2008
-
Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 238:10, s. 2761-2771
-
Tidskriftsartikel (refereegranskat)abstract
- Experimental data on component partitioning between suboxidized corium melt and steel in the invessel melt retention (IVR) conditions are compared. The data are produced within the OECD MASCAprogram and the ISTC CORPHAD project under close-to-isothermal conditions and in the ISTC METCORproject under thermal gradient conditions. Chemical equilibrium in the U–Zr–Fe(Cr,Ni,. . .)–O system isreached in all experiments. In MASCA tests the molten pool formed under inert atmosphere has twoimmiscible liquids, oxygen-enriched (oxidic) and oxygen-depleted (metallic), resulting of the miscibilitygap of the mentioned system. Sub-system data of the U–Zr–Fe(Cr,Ni,. . .)–O phase diagram investigatedwithin the ISTC CORPHAD project are interpreted in relation with the MASCA results. In METCOR teststhe equilibrium is established between oxidic liquid and mushy metallic part of the system. Results ofcomparison are discussed and the implications for IVR noted.
|
|
| 7. |
|
|
| 8. |
- Bechta, Sevostian, et al.
(författare)
-
Influence of corium oxidation on fission product release from molten pool
- 2010
-
Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 240:5, s. 1229-1241
-
Tidskriftsartikel (refereegranskat)abstract
- Qualitative and quantitative determination of the release of low-volatile fission products and core materialsfrom molten oxidic corium was investigated in the EVAN project under the auspices of ISTC. Theexperiments carried out in a cold crucible with induction heating and RASPLAV test facility are described.The results are discussed in terms of reactor application; in particular, pool configuration, melt oxidationkinetics, critical influence of melt surface temperature and oxidation index on the fission productrelease rate, aerosol particle composition and size distribution. The relevance of measured high releaseof Sr from the molten pool for the reactor application is highlighted. Comparisons of the experimentaldata with those from the COLIMA CA-U3 test and the VERCORS tests, as well as with predictions fromIVTANTHERMO and GEMINI/NUCLEA codes are made. Recommendations for further investigations areproposed following the major observations and discussions.
|
|
| 9. |
- Daskoulidou, Nikoleta, et al.
(författare)
-
High glucose enhances store-operated calcium entry by upregulating ORAI/STIM via calcineurin-NFAT signalling
- 2015
-
Ingår i: Journal of Molecular Medicine. - : Springer Science and Business Media LLC. - 1432-1440 .- 0946-2716. ; 93:5, s. 511-521
-
Tidskriftsartikel (refereegranskat)abstract
- ORAI and stromal interaction molecule (STIM) are storeoperated channel molecules that play essential roles in human physiology through a coupling mechanism of internal Ca2+ store to Ca2+ influx. However, the roles of ORAI and STIMin vascular endothelial cells under diabetic conditions remain unknown. Here, we investigated expression and signalling pathways of ORAI and STIM regulated by high glucose or hyperglycaemia using in vitro cell models, in vivo diabetic mice and tissues from patients. We found that ORAI1-3 and STIM1-2 were ubiquitously expressed in human vasculatures. Their expression was upregulated by chronic treatment with high glucose (HG, 25 mM D-glucose), which was accompanied by enhanced store-operated Ca2+ influx in vascular endothelial cells. The increased expression was also observed in the aortae from genetically modified Akita diabetic mice (C57BL/6-Ins2(Akita)/J) and streptozocin-induced diabetic mice, and aortae from diabetic patients. HG-induced upregulation of ORAI and STIM genes was prevented by the calcineurin inhibitor cyclosporin A and NFATc3 siRNA. Additionally, in vivo treatment with the nuclear factor of activated T cells (NFAT) inhibitor A-285222 prevented the gene upregulation in Akita mice. However, HG had no direct effects on ORAI1-3 currents and the channel activation process through cytosolic STIM1 movement in the cells coexpressing STIM1-EYFP/ORAIs. We concluded that upregulation of STIM/ORAI through Ca2+-calcineurin-NFAT pathway is a novel mechanism causing abnormal Ca2+ homeostasis and endothelial dysfunction under hyperglycaemia.
|
|
| 10. |
- Kotova, Natalia, et al.
(författare)
-
A novel micronucleus in vitro assay utilizing human hematopoietic stem cells
- 2015
-
Ingår i: Toxicology in Vitro. - : Elsevier BV. - 0887-2333 .- 1879-3177. ; 29:7, s. 1897-1905
-
Tidskriftsartikel (refereegranskat)abstract
- The induction of micronucleated reticulocytes in the bone marrow is a sensitive indicator of chromosomal damage. Therefore, the micronucleus assay in rodents is widely used in genotoxicity and carcinogenicity testing. A test system based on cultured human primary cells could potentially provide better prediction compared to animal tests, increasing patient safety while also implementing the 3Rs principle, i.e. replace, reduce and refine. Hereby, we describe the development of an in vitro micronucleus assay based on animal-free ex vivo culture of human red blood cells from hematopoietic stem cells. To validate the method, five clastogens with direct action, three clastogens requiring metabolic activation, four aneugenic and three non-genotoxic compounds have been tested. Also, different metabolic systems have been applied. Flow cytometry was used for detection and enumeration of micronuclei. Altogether, the results were in agreement with the published data and indicated that a sensitive and cost effective in vitro assay to assess genotoxicity with a potential to high-throughput screening has been developed.
|
|
