| 331. |
- Morgan, Ruth A., et al.
(författare)
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Carbonyl reductase 1 catalyzes 20 beta-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Carbonyl Reductase 1 (CBR1) is a ubiquitously expressed cytosolic enzyme important in exogenous drug metabolism but the physiological function of which is unknown. Here, we describe a role for CBR1 in metabolism of glucocorticoids. CBR1 catalyzes the NADPH-dependent production of 20 beta-dihydrocortisol (20 beta-DHF) from cortisol. CBR1 provides the major route of cortisol metabolism in horses and is up-regulated in adipose tissue in obesity in horses, humans and mice. We demonstrate that 20 beta-DHF is a weak endogenous agonist of the human glucocorticoid receptor (GR). Pharmacological inhibition of CBR1 in diet-induced obesity in mice results in more marked glucose intolerance with evidence for enhanced hepatic GR signaling. These findings suggest that CBR1 generating 20 beta-dihydrocortisol is a novel pathway modulating GR activation and providing enzymatic protection against excessive GR activation in obesity.
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| 332. |
- Nahari, G., et al.
(författare)
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'Language of lies': Urgent issues and prospects in verbal lie detection research
- 2019
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Ingår i: Legal and Criminological Psychology. - : Wiley. - 1355-3259 .- 2044-8333. ; 24:1, s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- Since its introduction into the field of deception detection, the verbal channel has become a rapidly growing area of research. The basic assumption is that liars differ from truth tellers in their verbal behaviour, making it possible to classify them by inspecting their verbal accounts. However, as noted in conferences and in private communication between researchers, the field of verbal lie detection faces several challenges that merit focused attention. The first author therefore proposed a workshop with the mission of promoting solutions for urgent issues in the field. Nine researchers and three practitioners with experience in credibility assessments gathered for 3 days of discussion at Bar-Ilan University (Israel) in the first international verbal lie detection workshop. The primary session of the workshop took place the morning of the first day. In this session, each of the participants had up to 10 min to deliver a brief message, using just one slide. Researchers were asked to answer the question: 'In your view, what is the most urgent, unsolved question/issue in verbal lie detection?' Similarly, practitioners were asked: 'As a practitioner, what question/issue do you wish verbal lie detection research would address?' The issues raised served as the basis for the discussions that were held throughout the workshop. The current paper first presents the urgent, unsolved issues raised by the workshop group members in the main session, followed by a message to researchers in the field, designed to deliver the insights, decisions, and conclusions resulting from the discussions.
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| 333. |
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| 334. |
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| 335. |
- Pansuriya, Twinkal C., et al.
(författare)
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Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:12, s. 1256-1261
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Tidskriftsartikel (refereegranskat)abstract
- Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). We report somatic heterozygous mutations in IDH1 (c.394C>T encoding an R132C substitution and c.395G>A encoding an R132H substitution) or IDH2 (c.516G>C encoding R172S) in 87% of enchondromas (benign cartilage tumors) and in 70% of spindle cell hemangiomas (benign vascular lesions). In total, 35 of 43 (81%) subjects with Ollier disease and 10 of 13 (77%) with Maffucci syndrome carried IDH1 (98%) or IDH2 (2%) mutations in their tumors. Fourteen of 16 subjects had identical mutations in separate lesions. Immunohistochemistry to detect mutant IDH1 R132H protein suggested intraneoplastic and somatic mosaicism. IDH1 mutations in cartilage tumors were associated with hypermethylation and downregulated expression of several genes. Mutations were also found in 40% of solitary central cartilaginous tumors and in four chondrosarcoma cell lines, which will enable functional studies to assess the role of IDH1 and IDH2 mutations in tumor formation.
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| 336. |
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| 337. |
- Pohjola, V, et al.
(författare)
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Effect of periodic melting on geochemical and isotopic signals in an ice core from Lomonosovfonna, Svalbard
- 2002
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Ingår i: J.Geophys.Res.. ; 107:D4, s. ACL 1-14
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Tidskriftsartikel (refereegranskat)abstract
- In this work we examine the quality of the atmospherically deposited signals in an ice core taken from a periodically melting ice field, Lomonosovfonna on central Spitsbergen, Svalbard. The aim is to investigate how much the atmospheric deposited signals in the stratigraphy of ice pack are changed by periodic melting of the ice. To determine the impact of this melting on the stratigraphy found in the ice core, we use three diagnostics: 1) Association between peak values in the ice chemical and isotopic record and ice facies type; 2) Number of “annual” cycles in these records compared with independently-determined number of years represented in the ice core; 3) Statistical comparison between the isotopic record in the ice core and the isotope records from coastal stations from the same region. We find that during warm summers as much as 50% of the annual accumulation may melt and percolate into the firn, and in a median year this decreases to ca. 25 %. As a consequence of percolation the most mobile acids show upto 50 % higher concentrations in bubble poor ice facies compared with facies that are less affected by melt. Most of the other chemical species are less affected than the strong acids, and the stable water isotopes show little evidence of mobility Annual, or bi-annual cycles are detected in most parameters, and the water isotope record has a comparable statistical distribution to isotopic records from coastal stations. We conclude that ice cores from sites like Lomonosovfonna preserve an useful environmental record despite melt events and percolation, where most parameters displays an annual, or in poor cases a bi-annual atmospheric signal.
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| 338. |
- Pohjola, V, et al.
(författare)
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Reconstruction of three centuries of annual accumulation rates based on the record of stable isotopes of water from Lomonosovfonna, Svalbard
- 2002
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Ingår i: Annals of glaciology. ; 35, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- We use the upper 81 m of the record of stable isotopes of water from a 122 m long ice core from Lomonosovfonna, central Spitsbergen, to construct an ice core chronology and the annual accumulation rates over the ice field. The isotope cycles are counted in the ice core record using a model that neglects short wavelength and low amplitude cycles. We find approximately the same number of ä18O cycles as years between known reference horizons, and assume these cycles represent annual cycles. Testing the validity of this assumption using cycles in äD shows that both records give similar numbers of cycles. Using the ä18O chronology, and de-compressing the accumulation records using the Nye flow model, we calculate the annual accumulation for the ice core site back to 1715 AD. We find that the average accumulation rate from 1715 to 1950 o was on average 0.30 m w.e. Accumulation rates increased ca. 25% during the later part of the 20th century to an average of 0.41 m w.e. for the period 1950 – 1997. The accumulation rates show highly significant 2.1 and 21 year periodicities, which gives credibility to our time scale.
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| 339. |
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| 340. |
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