| 1. |
- Galetin, Aleksandra, et al.
(författare)
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Membrane transporters in drug development and as determinants of precision medicine
- 2024
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Ingår i: NATURE REVIEWS DRUG DISCOVERY. - 1474-1776 .- 1474-1784.
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Forskningsöversikt (refereegranskat)abstract
- The effect of membrane transporters on drug disposition, efficacy and safety is now well recognized. Since the initial publication from the International Transporter Consortium, significant progress has been made in understanding the roles and functions of transporters, as well as in the development of tools and models to assess and predict transporter-mediated activity, toxicity and drug-drug interactions (DDIs). Notable advances include an increased understanding of the effects of intrinsic and extrinsic factors on transporter activity, the application of physiologically based pharmacokinetic modelling in predicting transporter-mediated drug disposition, the identification of endogenous biomarkers to assess transporter-mediated DDIs and the determination of the cryogenic electron microscopy structures of SLC and ABC transporters. This article provides an overview of these key developments, highlighting unanswered questions, regulatory considerations and future directions. Significant progress has been made in understanding the influence of membrane transporters in drug disposition and response. Here, the International Transporter Consortium provides an update on the current status of membrane transporters in drug development and regulatory requirements, discusses recent scientific advances in the field and highlights future directions and unanswered questions.
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| 2. |
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| 3. |
- Majka, Jaroslaw, et al.
(författare)
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Microdiamond discovered in the Seve Nappe (Scandinavian Caledonides) and its exhumation by the "vacuum-cleaner" mechanism
- 2014
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Ingår i: Geology. - 0091-7613 .- 1943-2682. ; 42:12, s. 1107-1110
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Tidskriftsartikel (refereegranskat)abstract
- When a continent collides with an island arc or other continent, continental crust of the subducted continent may be buried to depths exceeding 100 km, and exposed to pressures that can cause formation of coesite and diamond. This process leads to substantial density increase in SiO2-rich rocks and, in turn, to a reduction of the buoyancy of the subducted material, which should inhibit exhumation. Nevertheless, coesite- and diamond-bearing continental crustal rocks are known from several occurrences worldwide. We report on the discovery of microdiamond in kyanite-garnet gneiss from allochthonous metasediments of the Seve Nappe Complex in the Scandinavian Caledonides. Our discovery calls for general reconsideration of existing exhumation models of deeply subducted continental crust. We propose that the diamond-bearing rocks were subducted in an arc-continent collision setting, and their exhumation was facilitated by local pressure reduction resulting from extraction of the forearc lithospheric block.
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| 4. |
- Morokuma, Tomoki, et al.
(författare)
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OISTER optical and near-infrared monitoring observations of peculiar radio-loud active galactic nucleus SDSSJ110006.07+442144.3
- 2017
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Ingår i: Nippon Tenmon Gakkai obun kenkyu hokoku. - : Oxford University Press (OUP). - 0004-6264. ; 69:5
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Tidskriftsartikel (refereegranskat)abstract
- We present monitoring campaign observations at optical and near-infrared (NIR) wavelengths for a radio-loud active galactic nucleus (AGN) at z = 0.840, SDSSJ110006.07+442144.3 (hereafter, J1100+4421), which was identified during a flare phase in late 2014 February. The campaigns consist of three intensive observing runs from the discovery to 2015 March, mostly within the scheme of the OISTER collaboration. Optical-NIR light curves and simultaneous spectral energy distributions (SEDs) are obtained. Our measurements show the strongest brightening in 2015 March. We found that the optical-NIR SEDs of J1100+4421 show an almost steady shape despite the large and rapid intranight variability. This constant SED shape is confirmed to extend to similar to 5 mu m in the observed frame using the archival WISE data. Given the lack of absorption lines and the steep power-law spectrum of alpha(upsilon) similar to -1.4, where f(v) proportional to v(alpha upsilon), synchrotron radiation by a relativistic jet with no or small contributions from the host galaxy and the accretion disk seemsmost plausible as an optical-NIR emission mechanism. The steep optical-NIR spectral shape and the large amplitude of variability are consistent with this object being a low.peak jet-dominated AGN. In addition, sub-arcsecond resolution optical imaging data taken with Subaru Hyper Suprime-Cam does not show a clear extended component and the spatial scales are significantly smaller than the large extensions detected at radio wavelengths. The optical spectrum of a possible faint companion galaxy does not show any emission lines at the same redshift, and hence a merging hypothesis for this AGN-related activity is not supported by our observations.
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| 5. |
- Munke, Anna, et al.
(författare)
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Primordial Capsid and Spooled ssDNA Genome Structures Unravel Ancestral Events of Eukaryotic Viruses
- 2022
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Marine algae viruses are important for controlling microorganism communities in the marine ecosystem and played fundamental roles during the early events of viral evolution. Here, we have focused on one major group of marine algae viruses, the single-stranded DNA (ssDNA) viruses from the Bacilladnaviridae family. We present the capsid structure of the bacilladnavirus Chaetoceros tenuissimus DNA virus type II (CtenDNAV-II), determined at 2.4-Å resolution. A structure-based phylogenetic analysis supported the previous theory that bacilladnaviruses have acquired their capsid protein via horizontal gene transfer from a ssRNA virus. The capsid protein contains the widespread virus jelly-roll fold but has additional unique features; a third β-sheet and a long C-terminal tail. Furthermore, a low-resolution reconstruction of the CtenDNAV-II genome revealed a partially spooled structure, an arrangement previously only described for dsRNA and dsDNA viruses. Together, these results exemplify the importance of genetic recombination for the emergence and evolution of ssDNA viruses and provide important insights into the underlying mechanisms that dictate genome organization.IMPORTANCE Single-stranded DNA (ssDNA) viruses are an extremely widespread group of viruses that infect diverse hosts from all three domains of life, consequently having great economic, medical, and ecological importance. In particular, bacilladnaviruses are highly abundant in marine sediments and greatly influence the dynamic appearance and disappearance of certain algae species. Despite the importance of ssDNA viruses and the last couple of years' advancements in cryo-electron microscopy, structural information on the genomes of ssDNA viruses remains limited. This paper describes two important achievements: (i) the first atomic structure of a bacilladnavirus capsid, which revealed that the capsid protein gene presumably was acquired from a ssRNA virus in early evolutionary events; and (ii) the structural organization of a ssDNA genome, which retains a spooled arrangement that previously only been observed for double-stranded viruses.
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| 6. |
- Murayama, Yoshinobu, et al.
(författare)
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Softening of the Mouse Zona Pellucida during Oocyte Maturation
- 2013
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Ingår i: 2013 35TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC). - : IEEE. - 9781457702167 ; , s. 6834-6837
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Konferensbidrag (refereegranskat)abstract
- A change in the elasticity and the resistance to dissolution of the mouse zona pellucida (ZP) was quantitatively evaluated at immature germinal vesicle (GV), mature metaphase II (MII) and fertilized pronuclear (PN) stages. Young's modulus of the ZP was measured using a micro tactile sensor (MTS), a highly sensitive resonator-based sensor for a micro scale elasticity measurement. 0.25% alpha-chymotrypsin was used for the ZP dissolution assay. The results of measuring the ZP elasticity and the dissolution time clearly showed that the ZP softened during oocyte maturation and the ZP hardened after fertilization. The results indicate that the amount of the zona softening can be a criterion to evaluate oocyte quality for the selection of top quality mature oocyte before in vitro fertilization (IVF) treatment.
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