| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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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. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 6. |
- Zoller, P, et al.
(författare)
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Quantum information processing and communication - Strategic report on current status, visions and goals for research in Europe
- 2005
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Ingår i: European Physical Journal D. Atomic, Molecular, Optical and Plasma Physics. - : Springer Science and Business Media LLC. - 1434-6060 .- 1434-6079. ; 36:2, s. 203-228
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Tidskriftsartikel (refereegranskat)abstract
- We present an excerpt of the document "Quantum Information Processing and Communication: Strategic report on current status, visions and goals for research in Europe", which has been recently published in electronic form at the website of FET (the Future and Emerging Technologies Unit of the Directorate General Information Society of the European Commission, http://www.cordis.lu/ist/fet/qipc-sr.htm). This document has been elaborated, following a former suggestion by FET, by a committee of QIPC scientists to provide input towards the European Commission for the preparation of the Seventh Framework Program. Besides being a document addressed to policy makers and funding agencies (both at the European and national level), the document contains a detailed scientific assessment of the state-of-the-art, main research goals, challenges, strengths, weaknesses, visions and perspectives of all the most relevant QIPC sub-fields, that we report here.
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| 7. |
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| 8. |
- El-Seedi, Hesham, et al.
(författare)
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Biosynthesis, natural sources, dietary intake, pharmacokinetic properties, and biological activities of hydroxycinnamic acids
- 2012
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 60:44, s. 10877-10895
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Forskningsöversikt (refereegranskat)abstract
- Hydroxycinnamic acids are the most widely distributed phenolic acids in plants. Broadly speaking, they can be defined as compounds derived from cinnamic acid. They are present at high concentrations in many food products, including fruits, vegetables, tea, cocoa, and wine. A diet rich in hydroxycinnamic acids is thought to be associated with beneficial health effects such as a reduced risk of cardiovascular disease. The impact of hydroxycinnamic acids on health depends on their intake and pharmacokinetic properties. This review discusses their chemistry, biosynthesis, natural sources, dietary intake, and pharmacokinetic properties.
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| 9. |
- Baroffio, C. A., et al.
(författare)
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Combining plant volatiles and pheromones to catch two insect pests in the same trap : Examples from two berry crops
- 2018
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Ingår i: Crop Protection. - : ELSEVIER SCI LTD. - 0261-2194 .- 1873-6904. ; 109, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Most horticultural crops are attacked by more than one insect pest. As broad-spectrum chemical control options are becoming increasingly restricted, there is a need to develop novel control methods. Semiochemical attractants are available for three important horticultural pests, strawberry blossom weevil, Anthonomus rubi Herbst (Coleoptera: Curculionidae), European tarnished plant bug, Lygus rugulipennis Poppius (Hemiptera: Miridae) and raspberry beetle, Byturus tomentostts deGeer (Coleoptera: Byturidae). Traps targeting more than one pest species would be more practical and economical for both monitoring and mass trapping than traps for single-species. In this study we aimed to (1) improve the effectiveness of existing traps for insect pests in strawberry and raspberry crops by increasing catches of each species, and (2) test if attractants for two unrelated pest species could be combined to capture both in the same trap without decreasing the total catches. Field tests were carried out in four European countries and different combinations of semiochemicals were compared. A volatile from strawberry flowers, 1,4 dimethoxybenzene (DMB), increased the attractiveness of the aggregation pheromone to both sexes of A. rubi. The host-plant volatile, phenylacetaldehyde (PAA), increased the attraction of female L. rugulipennis to the sex pheromone, and, in strawberry, there was some evidence that adding DMB increased catches further. Traps baited with the aggregation pheromone of A. rubi, DMB, the sex pheromone of L rugulipennis and PAA attracted both target species to the same trap with no significant difference in catches compared to those single-species traps. In raspberry, catches in traps baited with a combination of A. rubi aggregation pheromone, DMB and the commercially available lure for B. tomentosus, based on raspberry flower volatiles, were similar to those in single-species traps. In both crops the efficiency of the traps still needs improvement, but the multi species traps are adequate for monitoring and should not lead to confusion for the user as the target species are easy to distinguish from each other.
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| 10. |
- 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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