| 1. |
- Ekblad, Torun, et al.
(författare)
-
Towards small molecule inhibitors of mono-ADP-ribosyltransferases
- 2015
-
Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 95, s. 546-551
-
Tidskriftsartikel (refereegranskat)abstract
- Protein ADP-ribosylation is a post-translational modification involved in DNA repair, protein degradation, transcription regulation, and epigenetic events. Intracellular ADP-ribosylation is catalyzed predominantly by ADP-ribosyltransferases with diphtheria toxin homology (ARTDs). The most prominent member of the ARTD family, poly(ADP-ribose) polymerase-1 (ARTD1/PARP1) has been a target for cancer drug development for decades. Current PARP inhibitors are generally non-selective, and inhibit the mono-ADP-ribosyltransferases with low potency. Here we describe the synthesis of acylated amino benzamides and screening against the mono-ADP-ribosyltransferases ARTD7/PARP15, ARTD8/PARP14, ARTD10/PARP10, and the poly-ADP-ribosyltransferase ARTD1/PARP1. The most potent compound inhibits ARTD10 with sub-micromolar IC50.
|
|
| 2. |
- Elofsson, Anna Katarina, 1983
(författare)
-
Climate Policy for Aviation - Analyses of measures at multiple levels
- 2019
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aviation sector is affected by local, national, multinational (EU) and/or global climate policies targeting domestic, intra-European and intercontinental flights in different and partly overlapping ways. The aim of this thesis is to strengthen further knowledge on climate policy for aviation at multiple governance levels and by doing so contribute to a more informed policy process. This work is done by analysing climate policy, by both qualitative document analysis and energy-economic modelling, concerning aviation. Our results show that actions to reduce aviation emissions are taken at all geographical levels of governance. On the local level, a surprisingly large share, more than a quarter, of the cities studied are taking policy initiatives to reduce aviation. Moreover, we have recognized that cities tend to choose the system boundary (consumption or territorial perspective) that results in the lowest reported emissions. The major perceived conflict of interest at the local level is economic growth vs reduced air travel. With limited authority within the local setting, such as in the case of aviation emissions, governing by ‘agenda setting’ can be an important channel for cities to express their concerns and support change at higher levels. On the national level, some countries have policies such as passenger taxes, biofuel blending mandates (from 2020 in Norway) and carbon taxes on jet fuel. National policies in a country within the European Economic Area (EEA) will overlap fully with CORSIA and/or the EU ETS, which adds challenges regarding additionality of the emissions said to be reduced due by the different policies. Further, there is a potential for national policies to be spread and thereby achieve cumulative emissions reduction.
|
|
| 3. |
- Elofsson, Anna Katarina, 1983, et al.
(författare)
-
Local Governance of Greenhouse Gas Emissions from Air Travel
- 2018
-
Ingår i: Journal of Environmental Policy and Planning. - 1523-908X .- 1522-7200. ; 20:5, s. 578-594
-
Tidskriftsartikel (refereegranskat)abstract
- Global greenhouse gas emissions from air travel (GHG-A) are on the rise, and projections point towards a rapid growth in the coming decades. This study aims to examine how local government (cities), addresses GHG-A in their Sustainable Energy Action Plans (SEAP). To fulfil this aim, over 200 SEAPs were analysed focusing on three issues: (1) Treatment of GHG-A in local emissions inventories; (2) Policy initiatives within this domain; and (3) The cities’ perceptions of the conflicts of interests. Results showed that more than half of the cities acknowledge the challenge of GHG-A, around one third include GHG-A in their emissions inventories, and more than one quarter have initiated policy interventions. To categorise these interventions, we have added a mode ‘governing by agenda setting’ to an existing analytical framework, ‘Modes of governing’. With their authority limited to the local setting, this mode of governing is a common channel for cities to push changes at higher levels.
|
|
| 4. |
- Elofsson, Ulla, et al.
(författare)
-
Pulmonary delivery of antimicrobial peptides
- 2015
-
Ingår i: ONdrugDelivery. - 2049-145X .- 2049-1468. ; 57, s. 4-7
-
Tidskriftsartikel (refereegranskat)abstract
- Anna Fureby, PhD, Group Manager & Senior Scientist, Life Science, and Ulla Elofsson, PhD, Senior Scientist, both of SP Technical Research Institute of Sweden, and Per Gerde, PhD, Chief Scientific Officer, Inhalation Sciences Sweden, discuss the serious problem of antibiotic resistance and the potential role of antimicrobial peptides in the treatment of resistant bacterial strains. For pulmonary infections, optimising the formulation and delivery method is a crucial factor for success.
|
|
| 5. |
|
|
| 6. |
- Larsson, Jörgen, 1966, et al.
(författare)
-
International and national climate policies for aviation: a review
- 2019
-
Ingår i: Climate Policy. - : Informa UK Limited. - 1752-7457 .- 1469-3062. ; 19:6, s. 787-799
-
Forskningsöversikt (refereegranskat)abstract
- Aviation constitutes about 2.5% of all energy-related CO2 emissions and in addition there are non-CO2 effects. In 2016, the ICAO decided to implement a Carbon Offsetting and Reduction Scheme for International Aviation (CORSIA) and in 2017 the EU decided on faster emission reductions in its Emissions Trading System (EU ETS), which since 2012 includes the aviation sector. The effects of these policies on the expected development of air travel emissions from 2017 to 2030 have been analyzed. For the sample country Sweden, the analysis shows that when emissions reductions in other sectors are attributed to the aviation sector as a result of the EU ETS and CORSIA, carbon emissions are expected to reduce by -0.8% per year (however if non-CO2 emissions are included in the analysis, then emissions will increase). This is much less than what is needed to achieve the 2 degrees C target. Our analysis of potential national aviation policy instruments shows that there are legally feasible options that could mitigate emissions in addition to the EU ETS and CORSIA. Distance-based air passenger taxes are common among EU Member States and through increased ticket prices these taxes can reduce demand for air travel and thus reduce emissions. Tax on jet fuel is an option for domestic aviation and for international aviation if bilateral agreements are concluded. A quota obligation for biofuels is a third option.
|
|
| 7. |
- Mojica, Sergio, 1987-, et al.
(författare)
-
Red Fluorescent Chlamydia trachomatis Applied to Live Cell Imaging and Screening for Antibacterial Agents
- 2018
-
Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we describe the application of a transformed Chlamydia trachomatis strain constitutively expressing the red fluorescent protein mCherry, to allow real-time monitoring of the infection cycle and screening for agents that block replication of C. trachomatis. The red fluorescent C. trachomatis strain was detected autonomously without antibody staining and was equally susceptible to doxycycline as the wild type strain. A high-throughput screening assay was developed using the transformed strain and automated fluorescence microscopy. The assay was used in a pilot screen of a 349 compound library containing natural products from Australian flora and fauna. Compounds with anti-chlamydial activity were tested for dose response and toxicity to host cells and two non-toxic compounds had 50% effective concentration (EC50) values in the low micromolar range. Natural products are valuable sources for drug discovery and the identified Chlamydia growth inhibition may be starting points for future drug development. Live cell imaging was used to visualize growth of the red fluorescent C. trachomatis strain over time. The screening assay reduced workload and reagents compared to an assay requiring immunostaining and could further be used to monitor the development of Chlamydia inclusions and anti-chlamydial effect in real time.
|
|
| 8. |
- Saleeb, Michael, et al.
(författare)
-
Natural product inspired library synthesis – Identification of 2,3-diarylbenzofuran and 2,3-dihydrobenzofuran based inhibitors of Chlamydia trachomatis
- 2018
-
Ingår i: European Journal of Medicinal Chemistry. - : Elsevier. - 0223-5234 .- 1768-3254. ; 143, s. 1077-1089
-
Tidskriftsartikel (refereegranskat)abstract
- A natural product inspired library was synthesized based on 2,3-diarylbenzofuran and 2,3-diaryl-2,3-dihydrobenzofuran scaffolds. The library of forty-eight compounds was prepared by utilizing Pd-catalyzed one-pot multicomponent reactions and ruthenium-catalyzed intramolecular carbenoid C-H insertions. The compounds were evaluated for antibacterial activity in a panel of test systems including phenotypic, biochemical and image-based screening assays. We identified several potent inhibitors that block intracellular replication of pathogenic Chlamydia trachomatis with IC50 ≤ 3 μM. These new C. trachomatis inhibitors can serve as starting points for the development of specific treatments that reduces the global burden of C. trachomatis infections.
|
|
| 9. |
- Saleeb, Michael, 1985-
(författare)
-
Towards novel antibacterials : Synthesis and identification of natural product inspired inhibitors of Chlamydia trachomatis and development of chemical probes targeting virulence of Pseudomonas aeruginosa
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance has evolved significantly to become one of the serious threats to public health today. Yet, the pipeline of new antibiotics is drying up and is lagging behind the challenging needs. As a contribution to this recurrent need for novel antibacterials, we applied multidisciplinary strategies to identify small-molecule antibacterials against Chlamydia trachomatis and antivirulence agents against Pseudomonas aeruginosa infections. These strategies included:1. Synthesis of a focused compounds library inspired by natural product scaffolds followed by phenotypic screening against Chlamydia trachomatis. (Paper I)(-)-Hopeaphenol is a polyphenol natural product that was identified as an antivirulence agent against Y. pseudotuberculosis and P. aeruginosa. Hopeaphenol core scaffold, 2,3-diaryl-2,3-dihydrobenzofuran, is ubiquitous in polyphenolic phytochemicals. In this thesis, a focused library of forty-eight compounds was synthesized based on 2,3-diarylbenzofuran and 2,3-diaryl-2,3- dihydrobenzofuran. The library was then explored for antibacterial properties in a number of screening assays and resulted in five novel antichlamydial compounds with inhibition potency down to sub-micromolar. The identified molecules also inhibited the growth of different clinical presentations of C. trachomatis, one of the most common sexually transmitted disease worldwide.2. Target-based screening against the P. aeruginosa virulence factor using enzymatic and biophysical assays. (Paper II-IV)P. aeruginosa is a Gram-negative opportunistic pathogen with remarkable antibiotic resistance that is associated with a wide range of clinical infections. An alternative strategy to develop novel and selective antibacterials is to target the bacterial virulence factors, i.e. the ability of the bacteria to promote disease, thus ‘disarming’ the pathogens instead of killing them. P. aeruginosa employs its virulence factor, the type III secretion system (T3SS), to inject toxins (e.g. ExoS) into the eukaryotic cytosol. In one part of this thesis, we utilized enzymatic assay and identified inhibitors against the P. aeruginosa T3S toxin (ExoS). A follow up structure-activity relationship analysis was established and resulted in five (low micromolar) inhibitors of ExoS ADP-ribosylation enzymatic activity. In another part, we used surface plasmon resonance biophysical assay and identified small molecule binders of T3S translocation protein (PcrV). The primary SAR analysis was established and showed the antivirulence properties of these molecules and the potential to expand them further as novel antibacterials.
|
|
| 10. |
- Åkerman, Jonas, 1964, et al.
(författare)
-
DN debatt: Beskatta flyget som bilen för att nå klimatmålen
- 2016
-
Ingår i: Dagens nyheter.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Klimatpåverkan från svenskarnas flygresande är nu lika stor som påverkan från allt bilresande i Sverige. Men flygsektorn betalar i dag avsevärt mindre än om den skulle beskattas som vägsektorn. Vi föreslår därför ett paket med klimatdeklaration, passagerarskatt och biobränsleavdrag, skriver tre miljöforskare.
|
|
