| 1. |
- Chen, Deliang, 1961, et al.
(författare)
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Summary of a workshop on extreme weather events in a warming world organized by the Royal Swedish Academy of Sciences
- 2020
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Ingår i: Tellus Series B-Chemical and Physical Meteorology. - : Stockholm University Press. - 1600-0889 .- 0280-6509. ; 72:1
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Tidskriftsartikel (refereegranskat)abstract
- Climate change is not only about changes in means of climatic variables such as temperature, precipitation and wind, but also their extreme values which are of critical importance to human society and ecosystems. To inspire the Swedish climate research community and to promote assessments of international research on past and future changes in extreme weather events against the global climate change background, the Earth Science Class of the Royal Swedish Academy of Sciences organized a workshop entitled 'Extreme weather events in a warming world' in 2019. This article summarizes and synthesizes the key points from the presentations and discussions of the workshop on changes in floods, droughts, heat waves, as well as on tropical cyclones and extratropical storms. In addition to reviewing past achievements in these research fields and identifying research gaps with a focus on Sweden, future challenges and opportunities for the Swedish climate research community are highlighted.
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| 2. |
- Cui, Liang, et al.
(författare)
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Four additional natural 7-deazaguanine derivatives in phages and how to make them
- 2023
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Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 51:17, s. 9214-9226
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Tidskriftsartikel (refereegranskat)abstract
- Bacteriophages and bacteria are engaged in a constant arms race, continually evolving new molecular tools to survive one another. To protect their genomic DNA from restriction enzymes, the most common bacterial defence systems, double-stranded DNA phages have evolved complex modifications that affect all four bases. This study focuses on modifications at position 7 of guanines. Eight derivatives of 7-deazaguanines were identified, including four previously unknown ones: 2 & PRIME;-deoxy-7-(methylamino)methyl-7-deazaguanine (mdPreQ(1)), 2 & PRIME;-deoxy-7-(formylamino)methyl-7-deazaguanine (fdPreQ(1)), 2 & PRIME;-deoxy-7-deazaguanine (dDG) and 2 & PRIME;-deoxy-7-carboxy-7-deazaguanine (dCDG). These modifications are inserted in DNA by a guanine transglycosylase named DpdA. Three subfamilies of DpdA had been previously characterized: bDpdA, DpdA1, and DpdA2. Two additional subfamilies were identified in this work: DpdA3, which allows for complete replacement of the guanines, and DpdA4, which is specific to archaeal viruses. Transglycosylases have now been identified in all phages and viruses carrying 7-deazaguanine modifications, indicating that the insertion of these modifications is a post-replication event. Three enzymes were predicted to be involved in the biosynthesis of these newly identified DNA modifications: 7-carboxy-7-deazaguanine decarboxylase (DpdL), dPreQ(1) formyltransferase (DpdN) and dPreQ(1) methyltransferase (DpdM), which was experimentally validated and harbors a unique fold not previously observed for nucleic acid methylases.
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| 3. |
- Snyder, Gretchen L., et al.
(författare)
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Preclinical profile of ITI-214, an inhibitor of phosphodiesterase 1, for enhancement of memory performance in rats
- 2016
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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 233:17, s. 3113-3124
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Therapeutic agents for memory enhancement in psychiatric disorders, such as schizophrenia, are urgently needed.Objective: The aim of this study is to characterize the preclinical profile of ITI-214, a potent inhibitor of phosphodiesterase 1 (PDE1).Methods: ITI-214 was assayed for inhibition of PDE1 versus other PDE enzyme families using recombinant human PDE enzymes and for off-target binding to 70 substrates (General SEP II diversity panel; Caliper Life Sciences). Effects of ITI-214 (0.1–10 mg/kg, po) on memory performance were assayed in rats using the novel object recognition (NOR) paradigm, with drug given at specified time points prior to or following exposure to objects in an open field. ITI-214 was evaluated for potential drug-drug interaction with risperidone in rats using conditioned avoidance response (CAR) and pharmacokinetic assessments.Results: ITI-214 inhibited PDE1A (Ki = 33 pmol) with >1000-fold selectivity for the nearest other PDE family (PDE4D) and displayed minimal off-target binding interactions in a 70-substrate selectivity profile. By using specific timing of oral ITI-214 administration, it was demonstrated in the NOR that ITI-214 is able to enhance acquisition, consolidation, and retrieval memory processes. All memory effects were in the absence of effects on exploratory behavior. ITI-214 did not disrupt the risperidone pharmacokinetic profile or effects in CAR.Conclusions: ITI-214 improved the memory processes of acquisition, consolidation, and retrieval across a broad dose range (0.1–10 mg/kg, po) without disrupting the antipsychotic-like activity of a clinical antipsychotic medication, specifically risperidone. Clinical development of ITI-214 is currently in progress.
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| 4. |
- Xie, S., et al.
(författare)
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A re-assessment of metal pollution in the Dexing mining area in Jiangxi province, China : current status, hydro-geochemical controls, and effectiveness of remediation practices
- 2022
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Ingår i: International Journal of Environmental Science and Technology. - : Springer Nature. - 1735-1472 .- 1735-2630. ; 19, s. 10707-10722
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Tidskriftsartikel (refereegranskat)abstract
- This study re-assess the environmental impacts of the Dexing copper mine (the largest open-pit copper mine in Asia) on the Lean river and its two tributaries (the Dawu river and Jishui river) in the Jiangxi province, China, with particular focus on metal pollution as well as the effectiveness and side-effects of remediation activities. Results show that the Dawu river and its mixing zone with the Lean river were still heavily influenced by acid mine drainage (AMD) and loaded with elevated levels of metals, in particular Mn, Ni, and Al whose concentrations were frequently above the health-based guideline values. Manganese and Ni in the AMD-impacted waters were predicted to occur as free ions or sulfate and carbonate complexes, and thus highly-toxic to living organisms. Although Al in the AMD-impacted waters was predicted to exist largely as colloidal hydroxides with low bioavailability, abundant formation of such nano-sized particles could impair the respiratory and circulatory systems of aquatic macro-invertebrates. The integration and comparison of the results from the current and previous studies show that the concentrations of several metals (Cu, Zn, and Cd) in the Dawu river decreased significantly after 2011-2012, during which several remediation practices were implemented (e.g., AMD neutralization, excavation of contaminated sediments in impounded rivers, and rehabilitation of mine tailings and open-pit slopes). This provides evidence that these remediation practices have effectively limited the dispersion of metals from the mining area. However, AMD neutralization greatly enhanced the release of sulfate, making the mining area an even more important sulfate source.
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