| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
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| 4. |
- Oprea, Tudor I, et al.
(författare)
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Unexplored therapeutic opportunities in the human genome
- 2018
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Ingår i: Nature Reviews Drug Discovery. - : Springer Science and Business Media LLC. - 1474-1776 .- 1474-1784. ; 17:5, s. 317-332
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Tidskriftsartikel (refereegranskat)abstract
- A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development.
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| 5. |
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| 6. |
- Boswell, M. T., et al.
(författare)
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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
- 2022
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
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| 10. |
- Jaenson, T. G. T., et al.
(författare)
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Evaluation of extracts and oils of mosquito (Diptera : Culicidae) repellent plants from Sweden and Guinea-Bissau
- 2006
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Ingår i: Journal of medical entomology. - : Oxford University Press (OUP). - 0022-2585 .- 1938-2928. ; 43:1, s. 113-119
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Tidskriftsartikel (refereegranskat)abstract
- In laboratory tests, ethyl acetate extracts of Hyptis, suaveolens Poit. from Guinea-Bissau and Rhododendon tomentosum (Stokes) H. Harmaja (formerly Ledum palustre L.) and Myrica gale L. significantly reduced probing activity of Aedes aegypti (L.). In the field in southern Sweden, extracts of leaves of R. tomentosum, M. gale, and Achillea millefolium L. significantly reduced biting by Aedes mosquitoes. Volatile compounds from M. gale, R. tomentosum, A. millefolium, and H. suaveolens were collected by solid phase microextraction (SPME). Alternatively, compounds in the plants were subjected to extraction by organic solvents of different polarities or by steam distillation and collection by SPME. Compounds collected were identified by gas chromatography-mass spectrometry. Leaves of H. suaveolens contained mainly beta-caryophyllene, bergamotene, and terpinolene. The volatile fraction of an ethyl acetate extract of H. suaveolens was collected by SPME and included beta-caryophyllene, (-) -sabinene, beta-pinene, limonene, alpha-pinene, and bergamotene. The main volatiles detected were alpha-pinene, alpha-phellandrene, myrcene, and limonene from M. gale leaves or inflorescences; pcymene, sabinene, and terpinyl acetate from leaves of R. tornentoston; and (-)-germacrene D, beta-pinene, sabinene, and alpha-pinene from A. millefolium leaves or inflorescences. The selected plant species contained numerous volatiles known to have insecticidal, acaricidal, pesticidal, and/orinsect repellent properties.
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