Browsing by Subject "synergy"

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  • Mgbeahuruike, Eunice Ego; Stålnacke, Milla; Vuorela, Heikki; Holm, Yvonne (2019)
    Microbial resistance to currently available antibiotics is a public health problem in the fight against infectious diseases. Most antibiotics are characterized by numerous side effects that may be harmful to normal body cells. To improve the efficacy of these antibiotics and to find an alternative way to minimize the adverse effects associated with most conventional antibiotics, piperine and piperlongumine were screened in combination with conventional rifampicin, tetracycline, and itraconazole to evaluate their synergistic, additive, or antagonistic interactions against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The fractional inhibitory concentration index was used to estimate the synergistic effects of various combination ratios of the piperamides and antibiotics against the bacterial and fungal strains. Both piperine and piperlongumine showed synergistic effects against S. aureus when combined at various ratios with rifampicin. Synergistic interaction was also observed with piperine in combination with tetracycline against S. aureus, while antagonistic interaction was recorded for piperlongumine and tetracycline against S. aureus. All the piperamide/antibacterial combinations tested against P. aeruginosa showed antagonistic effects, with the exception of piperine and rifampicin, which recorded synergistic interaction at a ratio of 9:1 rifampicin/piperine. No synergistic interaction was observed when the commercial compounds were combined with itraconazole and tested against C. albicans. The results showed that piperine and piperlongumine are capable of improving the effectiveness of rifampicin and tetracycline. Dosage combinations of these bioactive compounds with the antibiotics used may be a better option for the treatment of bacterial infections that aims to minimize the adverse effects associated with the use of these conventional antibacterial drugs.
  • Locatelli, Bruno; Pramova, Emilia; Di Gregorio, Monica; Brockhaus, Maria; Chávez , Dennis Armas; Tubbeh , Ramzi; Sotes, Juan; Perla, Javier (2020)
    Increasing attention is being given to integrating adaptation and mitigation in climate change policies. Policy network analysis is a way to explore connections between adaptation and mitigation, and the opportunities or barriers to effective integration between these two policy subdomains. This study explores climate governance and policy networks by examining collaboration and information flows in national policy processes in Peru, a country with an active climate change policy domain. In contrast to most climate policy network analyses, this study distinguishes adaptation and mitigation subdomains through a multiplex approach. We used ERGM (Exponential Random Graph Models) to explain the existence of information flows and collaborations among 76 key actors in climate change policy in Peru. We identified actors who could connect adaptation and mitigation subdomains. Results show a concentration of influence in national government actors, particularly in the mitigation subdomain, and the isolation of actor groups that matter for policy implementation, such as the private sector or subnational actors. Results highlight the predominance of mitigation over adaptation and the existence of actors well positioned to broker relationships between the subdomains. The top brokers across subdomains were, however, not only actors with high centrality and brokerage roles in the subdomains, but also several "unusual key players" that were not brokers in any of the two layers separately. Key policy insights • National government institutions are central actors in climate change policy networks in Peru, reflecting national ownership of the climate change issue. • Private sector organizations and subnational actors in Peru are the least involved in information sharing and collaboration on climate change. • Actors from different levels and sectors are active in both adaptation and mitigation, which is good for climate policy integration. • Actors with the capacity to bridge the two policy subdomains are not necessarily central to each subdomain but may be actors that close structural holes between subdomains.
  • Brunotte, Linda; Zheng, Shuyu; Mecate-Zambrano, Angeles; Tang, Jing; Ludwig, Stephan; Rescher, Ursula; Schloer, Sebastian (2021)
    The ongoing SARS-CoV-2 pandemic requires efficient and safe antiviral treatment strategies. Drug repurposing represents a fast and low-cost approach to the development of new medical treatment options. The direct antiviral agent remdesivir has been reported to exert antiviral activity against SARS-CoV-2. Whereas remdesivir only has a very short half-life time and a bioactivation, which relies on pro-drug activating enzymes, its plasma metabolite GS-441524 can be activated through various kinases including the adenosine kinase (ADK) that is moderately expressed in all tissues. The pharmacokinetics of GS-441524 argue for a suitable antiviral drug that can be given to patients with COVID-19. Here, we analyzed the antiviral property of a combined treatment with the remdesivir metabolite GS-441524 and the antidepressant fluoxetine in a polarized Calu-3 cell culture model against SARS-CoV-2. The combined treatment with GS-441524 and fluoxetine were well-tolerated and displayed synergistic antiviral effects against three circulating SARS-CoV-2 variants in vitro in the commonly used reference models for drug interaction. Thus, combinatory treatment with the virus-targeting GS-441524 and the host-directed drug fluoxetine might offer a suitable therapeutic treatment option for SARS-CoV-2 infections.
  • Sugano, Junko; Maina, Ndegwa; Wallenius, Janne; Hilden, Kristiina (2021)
    Wood decomposition is a sophisticated process where various biocatalysts act simultaneously and synergistically on biopolymers to efficiently break down plant cell walls. In nature, this process depends on the activities of the wood-inhabiting fungal communities that co-exist and interact during wood decay. Wood-decaying fungal species have traditionally been classified as white-rot and brown-rot fungi, which differ in their decay mechanism and enzyme repertoire. To mimic the species interaction during wood decomposition, we have cultivated the white-rot fungus, Bjerkandera adusta, and two brown-rot fungi, Gloeophyllum sepiarium and Antrodia sinuosa, in single and co-cultivations on softwood and hardwood. We compared their extracellular hydrolytic carbohydrate-active and oxidative lignin-degrading enzyme activities and production profiles. The interaction of white-rot and brown-rot species showed enhanced (hemi)cellulase activities on birch and spruce-supplemented cultivations. Based on the enzyme activity profiles, the combination of B. adusta and G. sepiarium facilitated birch wood degradation, whereas B. adusta and A. sinuosa is a promising combination for efficient degradation of spruce wood, showing synergy in beta-glucosidase (BGL) and alpha-galactosidase (AGL) activity. Synergistic BGL and AGL activity was also detected on birch during the interaction of brown-rot species. Our findings indicate that fungal interaction on different woody substrates have an impact on both simultaneous and sequential biocatalytic activities.
  • Chia, Eugene L.; Fobissie Blese, Kalame; Kanninen, Markku (2016)
    There is growing interest in designing and implementing climate change mitigation and adaptation (M + A) in synergy in the forest and land use sectors. However, there is limited knowledge on how the planning and promotion of synergies between M + A can be operationalized in the current efforts to mitigate climate change through forest carbon. This paper contributes to fill this knowledge gap by exploring ways of planning and promoting M + A synergy outcomes in forest carbon initiatives. It examines eight guidelines that are widely used in designing and implementing forest carbon initiatives. Four guiding principles with a number of criteria that are relevant for planning synergy outcomes in forest carbon activities are proposed. The guidelines for developing forest carbon initiatives need to demonstrate that (1) the health of forest ecosystems is maintained or enhanced; (2) the adaptive capacity of forest-dependent communities is ensured; (3) carbon and adaptation benefits are monitored and verified; and (4) adaptation outcomes are anticipated and planned in forest carbon initiatives. The forest carbon project development guidelines can encourage the integration of adaptation in forest carbon initiatives. However, their current efforts guiding projects and programs to deliver biodiversity and environmental benefits, ecosystem services, and socioeconomic benefits are not considered explicitly as efforts towards enhancing adaptation. An approach for incentivizing and motivating project developers, guideline setters, and offset buyers is imperative in order to enable existing guidelines to make clear contributions to adaptation goals. We highlight and discuss potential ways of incentivizing and motivating the explicit planning and promotion of adaptation outcomes in forest carbon initiatives.
  • Cosens, Barbara; Ruhl, J. B.; Soininen, Niko; Gunderson, Lance; Belinskij, Antti; Blenckner, Thorsten; Camacho, Alejandro E.; Chaffin, Brian C.; Craig, Robin Kundis; Doremus, Holly; Glicksman, Robert; Heiskanen, Anna-Stiina; Larson, Rhett; Similä, Jukka (National Academy of Sciences, 2021)
    Proceedings of the National Academy of Sciences Sep 2021, 118 (36) e2102798118
    The speed and uncertainty of environmental change in the Anthropocene challenge the capacity of coevolving social–ecological–technological systems (SETs) to adapt or transform to these changes. Formal government and legal structures further constrain the adaptive capacity of our SETs. However, new, self-organized forms of adaptive governance are emerging at multiple scales in natural resource-based SETs. Adaptive governance involves the private and public sectors as well as formal and informal institutions, self-organized to fill governance gaps in the traditional roles of states. While new governance forms are emerging, they are not yet doing so rapidly enough to match the pace of environmental change. Furthermore, they do not yet possess the legitimacy or capacity needed to address disparities between the winners and losers from change. These emergent forms of adaptive governance appear to be particularly effective in managing complexity. We explore governance and SETs as coevolving complex systems, focusing on legal systems to understand the potential pathways and obstacles to equitable adaptation. We explore how governments may facilitate the emergence of adaptive governance and promote legitimacy in both the process of governance despite the involvement of nonstate actors, and its adherence to democratic values of equity and justice. To manage the contextual nature of the results of change in complex systems, we propose the establishment of long-term study initiatives for the coproduction of knowledge, to accelerate learning and synergize interactions between science and governance and to foster public science and epistemic communities dedicated to navigating transitions to more just, sustainable, and resilient futures.
  • Herring, Shawn; Oda, Jessica M.; Wagoner, Jessica; Kirchmeier, Delaney; O'Connor, Aidan; Nelson, Elizabeth A.; Huang, Qinfeng; Liang, Yuying; DeWald, Lisa Evans; Johansen, Lisa M.; Glass, Pamela J.; Olinger, Gene G.; Ianevski, Aleksandr; Aittokallio, Tero; Paine, Mary F.; Fink, Susan L.; White, Judith M.; Polyak, Stephen J. (2021)
    Neglected diseases caused by arenaviruses such as Lassa virus (LASV) and filoviruses like Ebola virus (EBOV) primarily afflict resource-limited countries, where antiviral drug development is often minimal. Previous studies have shown that many approved drugs developed for other clinical indications inhibit EBOV and LASV and that combinations of these drugs provide synergistic suppression of EBOV, often by blocking discrete steps in virus entry. We hypothesize that repurposing of combinations of orally administered approved drugs provides effective suppression of arenaviruses. In this report, we demonstrate that arbidol, an approved influenza antiviral previously shown to inhibit EBOV, LASV, and many other viruses, inhibits murine leukemia virus (MLV) reporter viruses pseudotyped with the fusion glycoproteins (GPs) of other arenaviruses (Junin virus (JUNV], lymphocytic choriomeningitis virus (LCMV), and Pichinde virus (PICA). Arbidol and other approved drugs, including aripiprazole, amodiaquine, sertraline, and niclosamide, also inhibit infection of cells by infectious PICV, and arbidol, sertraline, and niclosamide inhibit infectious LASV. Combining arbidol with aripiprazole or sertraline results in the synergistic suppression of LASV and JUNV GP-bearing pseudoviruses. This proof-of-concept study shows that arenavirus infection in vitro can be synergistically inhibited by combinations of approved drugs. This approach may lead to a proactive strategy with which to prepare for and control known and new arenavirus outbreaks.
  • Heinilä, Lassi; Fewer, David; Jokela, Jouni; Wahlsten, Matti; Jortikka, Anna Elisabeth; Sivonen, Kaarina (2020)
    Cyanobacteria produce a wide range of lipopeptides that exhibit potent membrane-disrupting activities. Laxaphycins consist of two families of structurally distinct macrocyclic lipopeptides that act in a synergistic manner to produce antifungal and antiproliferative activities. Laxaphycins are produced by range of cyanobacteria but their biosynthetic origins remain unclear. Here, we identified the biosynthetic pathways responsible for the biosynthesis of the laxaphycins produced by Scytonema hofmannii PCC 7110. We show that these laxaphycins, called scytocyclamides, are produced by this cyanobacterium and are encoded in a single biosynthetic gene cluster with shared polyketide synthase enzymes initiating two distinct non-ribosomal peptide synthetase pathways. The unusual mechanism of shared enzymes synthesizing two distinct types of products may aid future research in identifying and expressing natural product biosynthetic pathways and in expanding the known biosynthetic logic of this important family of natural products.