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Kishan?Kumar Chudasama Jonathon Winnay Stefan Johansson Tor Claudi Rainer K?nig Ingfrid Haldorsen Bente Johansson Ju?Rang Woo Dagfinn Aarskog J?rn?V. Sagen C.?Ronald Kahn Anders Molven P?l?Rasmus Nj?lstad 《American journal of human genetics》2013,93(1):150-157
The phosphatidylinositol 3 kinase (PI3K) pathway regulates fundamental cellular processes such as metabolism, proliferation, and survival. A central component in this pathway is the p85α regulatory subunit, encoded by PIK3R1. Using whole-exome sequencing, we identified a heterozygous PIK3R1 mutation (c.1945C>T [p.Arg649Trp]) in two unrelated families affected by partial lipodystrophy, low body mass index, short stature, progeroid face, and Rieger anomaly (SHORT syndrome). This mutation led to impaired interaction between p85α and IRS-1 and reduced AKT-mediated insulin signaling in fibroblasts from affected subjects and in reconstituted Pik3r1-knockout preadipocytes. Normal PI3K activity is critical for adipose differentiation and insulin signaling; the mutated PIK3R1 therefore provides a unique link among lipodystrophy, growth, and insulin signaling. 相似文献
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Sylvi Haldorsen Hasan Akan Bahattin ?elik Manfred Heun 《Vegetation History and Archaeobotany》2011,20(4):305-318
The domestication of the Neolithic founder crops of the Near East has recently been a topic of debate particularly with respect
to how rapidly the domestication of these crops occurred. One school of thought maintains that these processes lasted several
thousand years (‘protracted model’ with ‘gathering’, ‘cultivation’ and ‘domestication’ as three stages of a continuum, each
taking up to several thousand years), while another favors the view that domestication occurred much more quickly, over several
hundred years at most (‘rapid transition’). Our study focuses on one of these crops, 1-grained domesticated Einkorn wheat,
incorporating data from geology, vegetation history, and climate. In the Karacadağ region of southeastern Turkey, where 1-grained
Einkorn wheat was domesticated, the climate was severe (i.e. cold and dry) during the Younger Dryas. The climate of the Younger
Dryas acted as boundary during which a) conditions were not suitable for ‘cultivation’, and b) Einkorn would have retreated
to refugia exhibiting more suitable moisture-bearing soils that would have made ‘gathering’ difficult. Around 11600 cal. b.p., the Younger Dryas ended and a very rapid climatic amelioration commenced at the beginning of the Early Holocene, enabling
grasses to spread throughout the region. A ritual PPNA/PPNB site (G?bekli Tepe) and associated PPNB settlements such as Nevali
?ori and ?ay?nü were established at this time. In the settlements of Nevali ?ori and Cafer H?yük, the oldest domesticated
Einkorn was found in the earliest archaeological layers. This confirms that the inhabitants made use of domesticated 1-grained
Einkorn from the very beginning of settlement activity, although they continued to practice a mixed lifestyle as hunter-gatherers
and farmers. For ?ay?nü the issue is more complex, but here domesticated Einkorn also appears around the same time. In summary,
by 10400 cal. b.p. domesticated 1-grained Einkorn was present in large quantities at a variety of sites. This would give a maximum window of
time lasting approximately 1,200 years and is therefore not in agreement with the ‘protracted’ model but would be consistent
with a ‘rapid transition’. It is improbable that the ‘cultivation’ of wild Einkorn was practiced in the Karacadağ region,
since wild Einkorn was plentiful during the favorable growing conditions following the Younger Dryas, making it more likely
that ‘gathering’ would have been practiced. Because Einkorn has not been found in early settlements in the southern Levant,
this crop cannot have been ‘gathered’ and ‘cultivated’ there but instead was ‘domesticated’ independently and solely in southeastern
Turkey. Therefore, the YD acts as a boundary, providing a maximum time frame for 1-grained Einkorn domestication. 相似文献
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Lourdes López‐Merino Suzanne A. G. Leroy Sylvi Haldorsen Manfred Heun Alan Reynolds 《Botanical journal of the Linnean Society. Linnean Society of London》2015,177(2):278-289
The domestication of the one‐grained einkorn (Triticum monococcum) in the Near East is relatively well known. However, an independent two‐grained einkorn‐like domestication has been archaeobotanically detected and scarce information is available. Triticum urartu, a wild wheat, was not fully described until the 1970s because the phenology does not allow it to be distinguished easily from wild einkorn (Triticum boeoticum subsp. thaoudar), although a genetic separation exists. Both species are mostly two grained and could potentially be the relatives of the extinct two‐grained form. Pollen grains of several genetically well‐identified wheat species, including T. urartu and T. boeoticum subsp. thaoudar, were studied by measuring the grain diameter and examining the exine sculpturing with phase‐contrast microscopy and scanning electron microscopy to gain an insight into differences enabling taxonomic identification. This work showed that, although T. urartu pollen is smaller on average, grain diameter is not sufficient because of the size overlap between the species, but T. urartu presents a different exine sculpturing (scabrate) from other Triticum spp. (aerolate). This outcome is useful for taxonomists and archaeobotanists. First, it will allow a simple re‐classification of herbarium materials. Second, further research could establish whether T. urartu was cultivated. © 2015 The Linnean Society of London, Botanical Journal of the Linnean Society, 2015, 177 , 278–289. 相似文献
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Introduction
Fatigue is prevalent in primary Sj?gren's syndrome (pSS), and contributes to the considerably reduced health related quality of life in this disease. The symptom is included in proposed disease activity and outcome measures for pSS. Several studies indicate that there is an inflammatory component of fatigue in pSS and other chronic inflammatory rheumatic diseases. The purpose of this study was to investigate fatigue change in pSS in a longitudinal study, and explore whether any clinical or laboratory variables at baseline, including serum cytokines, were associated with a change in fatigue scores over time. 相似文献6.
Arnt Inge Vistnes Gro B. Ramberg Lars Rune Bjrnevik Tore Tynes Tor Haldorsen 《Bioelectromagnetics》1997,18(1):47-57
The aim of this work was to study the exposure to magnetic fields of children living at different distances from a power line and to evaluate how well theoretical calculations compared with actual exposure. Personal exposure instruments were carried for 24 h by 65 schoolchildren living 28–325 m from a 300 kV transmission line; the current load was 200–700 A. About half of the children attended a school far from the power line, whereas the other half attended a school located about 25 m from the line. Exposure to magnetic fields was analyzed for three categories of location: at home, at school, and at all other places. Time spent in bed was analyzed separately. The results indicated that children who lived close to a power line had a higher magnetic field exposure than other children. The power line was the most important source of exposure when the magnetic field due to the line was greater than about 0.2 μT. Exposure at school influenced the 24 h time-weighted average results considerably in those cases where the distance between home and power line was very different from the distance between school and power line. The calculated magnetic field, based on line configuration, current load, and distance between home and power line, corresponded reasonably well with the measured field. However, the correlation depends on whether home only or 24 h exposure is used in the analysis and on which school the children attended. The calculated magnetic field seems to be a reasonably good predictor of actual exposure and could be used in epidemiological studies, at least in Norway, where the electrical system normally results in less ground current than in most other countries. Bioelectromagnetics 18:47–57, 1997. © 1997 Wiley-Liss, Inc. 相似文献
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Ingfrid S. Haldorsen Mihaela Popa Tina Fonnes Nj?l Brekke Reidun Kopperud Nicole C. Visser Cecilie B. Rygh Tina Pavlin Helga B. Salvesen Emmet McCormack Camilla Krakstad 《PloS one》2015,10(8)
Background
Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy.Methods
After orthotopic injection with luc-expressing endometrial cancer cells, eleven mice developed disease detected by weekly bioluminescence imaging (BLI). In parallel the same mice underwent positron emission tomography–computed tomography (PET-CT) and magnetic resonance imaging (MRI) employing 18F-fluorodeoxyglocose (18F-FDG) or 18F- fluorothymidine (18F-FLT) and contrast reagent, respectively. The mice were sacrificed when moribund, and post-mortem examination included macroscopic and microscopic examination for validation of growth of primary uterine tumours and metastases. PET-CT was also performed on a patient derived model (PDX) generated from a patient with grade 3 endometrioid endometrial cancer.Results
Increased BLI signal during tumour growth was accompanied by increasing metabolic tumour volume (MTV) and increasing MTV x mean standard uptake value of the tumour (SUVmean) in 18F-FDG and 18F-FLT PET-CT, and MRI conspicuously depicted the uterine tumour. At necropsy 82% (9/11) of the mice developed metastases detected by the applied imaging methods. 18F-FDG PET proved to be a good imaging method for detection of patient derived tumour tissue.Conclusions
We demonstrate that all imaging modalities enable monitoring of tumour growth and metastatic spread in an orthotopic mouse model of endometrial carcinoma. Both PET tracers, 18F-FDG and 18F-FLT, appear to be equally feasible for detecting tumour development and represent, together with MRI, promising imaging tools for monitoring of patient-derived xenograft (PDX) cancer models. 相似文献8.
To reassess domestication events in the Near East, accessions of Triticum urartu from a well-described sampling were combined with a representative sample covering the Karacada? Einkorn wheat domestication. The observed DNA separation between the two wheat species accounts for the main differentiation, but geographic variation within T. urartu is evident and so is the domestication scenario among wild, feral, and domesticated Einkorn. In contrast to the clear DNA differences, it is difficult to separate living T. urartu from wild Einkorn based on morphology. With archaeobotanical material a distinction of carbonized remains of these two wheats is considered to be impossible. We reviewed the differences concerning morphology and maturity and combined these observations with information about archaeological sites in the Near East. In conclusion, the excavation sites in the middle Euphrates may contain T. urartu rather than Einkorn wheat and T. urartu may underlie the reported occurrence of the extinct 2-grained domesticated "Einkorn" wheat. The first Einkorn wheat domestication sensu stricto seems to have happened around the Karacada?, as reported earlier. The human dimension shown by the excavation of G?bekli Tepe can explain why domesticated phenotypes might have spread quickly. 相似文献
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Aldoses are degraded by vanadium pentaoxide in m sulphuric acid into formic acid and the next lower aldose, and aldonic acids are degraded into carbon dioxide and the next lower aldose. Each reaction consumes two equivalents of oxidant. Glycoaldehyde is oxidized to formic acid via glyoxal, and glycolic acid is oxidized to carbon dioxide and formic acid via glyoxylic acid. 相似文献
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