A new heparan sulfate from the mollusk nodipecten nodosus inhibits merozoite invasion and disrupts rosetting and cytoadherence of plasmodium falciparum

Despite treatment with effective antimalarial drugs, the mortality rate is still high in severe cases of the disease, highlighting the need to find adjunct therapies that can inhibit the adhesion of Pf-iEs. In this context, we evaluated a new heparan sulfate (HS) from Nodipecten nodosus for antimalarial activity and inhibition of P. falciparum cytoadhesion and rosetting. Parasite inhibition was measured by SYBR green using a cytometer. HS was assessed in rosetting and cytoadhesion assays under static and flow conditions using CHO and HLEC cells expressing ICAM1 and CSA, respectively. This HS inhibited merozoite invasion similar to heparin. Moreover, mollusk HS decreased cytoadherence of P. falciparum to CSA (chondroitin sulfate A) and ICAM-1 (intercellular adhesion molecule-1) on the surface of endothelial cells under static and flow conditions. In addition, this glycan efficiently disrupted rosettes. These findings support a potential use for mollusk HS as adjunct therapy for severe malaria114CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPnão temnão tem2012/16525-2; 2017/18611-7; 2010/18571-6; 2015/20774-

Framework for Climate Change Adaptation of Agriculture and Forestry in Mediterranean Climate Regions

Planning the adaptation of agriculture and forestry landscapes to climate change remains challenging due to the need for integrating substantial amounts of information. This information ranges from climate scenarios, geographical site information, socio-economic data and several possible adaptation measures. Thus, there is an urgent need to have a framework that is capable of organizing adaptation strategies and measures in the agriculture and forestry sectors in Mediterranean climatic regions. Additionally, this framework should provide a cause effect relation with climate vulnerability to adequately support the development of adaptation planning at municipal and local (farm) level. In this context, we propose to test and evaluate a framework for climate adaptation of the agriculture and forestry sectors, based on the local causal-effect relation between adaptation strategies and measures and the level of vulnerability reduction achieved for Mediterranean areas. The framework was developed based on the combination of the DPSIR (Driving forces, Pressures, State, Impacts, Responses) and Vulnerability frameworks and reviewed 162 practical adaptation measures, further organized into strategies, complemented by a set of efficacy indicators. The framework was tested with 70 stakeholders in six stakeholder workshops for the planning of two farms and one municipal climate adaptation study, that are now in actual implementation and monitoring. The framework is composed by a set of eight adaptation strategies in which adaptation measures are clustered and assessed using efficacy indicators. In the evaluation of the adaptation framework, 96% of stakeholders considered its content as good or very good and 89% considered the final outcomes as good or very good. Finally, the framework was also used to assess and compare the adaptation strategies and measures presented in the climate adaptation plans of the three case studies. On average, 52.2% of the adaptation measures selected by the three case studies are dedicated to Ecosystem Resilience, 30.9% to Adaptive Capacity, 9.1% to Microclimates, 7.4% to Protection, and 0.3% to Mitigation strategies. This framework was considered effective in supporting adaptation planning at farm and municipal levels and useful to assess and compare adaptation plans in the frame of vulnerability reduction. Future studies can further contribute to support adaptation planning in these sectors by using, developing and streamlining this framework to additional and different socio-ecological contextsinfo:eu-repo/semantics/publishedVersio

Chloroquine: Modes Of Action Of An Undervalued Drug

For more than two decades, chloroquine (CQ) was largely and deliberately used as first choice drug for malaria treatment. However, worldwide increasing cases of resistant strains of Plasmodium have hampered its use. Nevertheless, CQ has recently been tested as adjunct therapy in several inflammatory situations, such as rheumatoid arthritis and transplantation procedures, presenting intriguing and promising results. 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Antibody Recognition Of Plasmodium Falciparum Infected Red Blood Cells By Symptomatic And Asymptomatic Individuals In The Brazilian Amazon

In the Amazon Region, there is a virtual absence of severe malaria and few fatal cases of naturally occurring Plasmodium falciparum infections; this presents an intriguing and underexplored area of research. In addition to the rapid access of infected persons to effective treatment, one cause of this phenomenon might be the recognition of cytoadherent variant proteins on the infected red blood cell (IRBC) surface, including the var gene encoded P. falciparum erythrocyte membrane protein 1. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms.1095598607Albrecht, L., Castiñeiras, C., Carvalho, B.O., Ladeia-Andrade, S., da Silva, N.S., Hoffmann, E.H.E., dalla Martha, R.C., Wunderlich, G., The South American Plasmodium falciparum var gene repertoire is limited, highly shared and possibly lacks several antigenic types (2010) Gene, 453, pp. 37-44Albrecht, L., Merino, E.F., Hoffmann, E.H.E., Ferreira, M.U., Ferreira, R.G.M., Osakabe, A.L., dalla Martha, R.C., Wunderlich, G., Extense variant gene family repertoire overlap in western Amazon Plasmodium falciparum isolates (2006) Mol Biochem Parasitol, 150, pp. 157-165Altschul, S.F., Madden, T.L., Schäffer, A.A., Zhang, J., Zhang, Z., Miller, W., Lipman, D.J., Gapped BLAST and PSI-BLAST: A new generation of protein database search programs (1997) Nucleic Acids Res, 25, pp. 3389-3402Alves, F.P., Durlacher, R.R., Menezes, M.J., Krieger, H., Silva, L.H., Camargo, E.P., High prevalence of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in native Amazonian populations (2002) Am J Trop Med Hyg, 66, pp. 641-648Anderson, T.J., Su, X.Z., Bockarie, M., Lagog, M., Day, K.P., Twelve microsatellite markers for characterization of Plasmodium falciparum from finger-prick blood samples (1999) Parasitology, 119, pp. 113-125Andrews, K.T., Adams, Y., Viebig, N.K., Lanzer, M., Schwartz-Albiez, R., Adherence of Plasmodium falciparum infected erythrocytes to CHO-745 cells and inhibition of binding by protein A in the presence of human serum (2005) Int J Parasitol, 35, pp. 1127-1134Avril, M., Tripathi, A.K., Brazier, A.J., Andisi, C., Janes, J.H., Soma, V.L., Sullivan, D.J., Smith, J.D., A restricted subset of var genes mediates adherence of Plasmodium falciparum-infected erythrocytes to brain endothelial cells (2012) Proc Natl Acad Sci USA, 109, pp. 1782-1790Baruch, D.I., Pasloske, B.L., Singh, H.B., Bi, X., Ma, X.C., Feldman, M., Taraschi, T.F., Howard, R.J., Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes (1995) Cell, 82, pp. 77-87Bengtsson, A., Joergensen, L., Rask, T.S., Olsen, R.W., Andersen, M.A., Turner, L., Theander, T.G., Jensen, A.T.R., A novel domain cassette identifies Plasmodium falciparum PfEMP1 proteins binding ICAM-1 and is a target of cross-reactive, adhesion-inhibitory antibodies (2013) J Immunol, 190, pp. 240-249Bull, P.C., Berriman, M., Kyes, S., Quail, M.A., Hall, N., Kortok, M.M., Marsh, K., Newbold, C.I., Plasmodium falciparum variant surface antigen expression patterns during malaria (2005) PLoS Pathog, 1, pp. e26Bull, P.C., Kyes, S., Buckee, C.O., Montgomery, J., Kortok, M.M., Newbold, C.I., Marsh, K., An approach to classifying sequence tags sampled from Plasmodium falciparum var genes (2007) Mol Biochem Parasitol, 154, pp. 98-102Bull, P.C., Lowe, B.S., Kortok, M., Molyneux, C.S., Newbold, C.I., Marsh, K., Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria (1998) Nat Med, 4, pp. 358-360Chan, J.-A., Howell, K.B., Reiling, L., Ataide, R., Mackintosh, C.L., Fowkes, F.J.I., Petter, M., Beeson, J.G., Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity (2012) J Clin Invest, 122, pp. 3227-3238Claessens, A., Adams, Y., Ghumra, A., Lindergard, G., Buchan, C.C., Andisi, C., Bull, P.C., Rowe, J.A., A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells (2012) Proc Natl Acad Sci USA, 109, pp. 1772-1781Crompton, P.D., Kayala, M.A., Traore, B., Kayentao, K., Ongoiba, A., Weiss, G.E., Molina, D.M., Pierce, S.K., A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray (2010) Proc Natl Acad Sci USA, 107, pp. 6958-6963Freitas-Júnior, L.H., Bottius, E., Pirrit, L.A., Deitsch, K.W., Scheidig, C., Guinet, F., Nehrbass, U., Scherf, A., Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum (2000) Nature, 407, pp. 1018-1022Golnitz, U., Albrecht, L., Wunderlich, G., Var transcription profiling of Plasmodium falciparum 3D7: Assignment of cytoadherent phenotypes to dominant transcripts (2008) Malar J, 7, p. 14Guizetti, J., Scherf, A., Silence, activate, poise and switch! Mechanisms of antigenic variation in Plasmodium falciparum (2013) Cell Microbiol, 15, pp. 718-726Hasler, T., Albrecht, G.R., van Schravendijk, M.R., Aguiar, J.C., Morehead, K.E., Pasloske, B.L., Ma, C., Howard, R.J., An improved microassay for Plasmodium falciparum cytoadherence using stable transformants of Chinese hamster ovary cells expressing CD36 or intercellular adhesion molecule-1 (1993) Am J Trop Med Hyg, 48, pp. 332-347Hviid, L., Naturally acquired immunity to Plasmodium falcipa-rum malaria in Africa (2005) Acta Trop, 95, pp. 270-275Joergensen, L., Bengtsson, D.C., Bengtsson, A., Ronander, E., Berger, S.S., Turner, L., Dalgaard, M.B., Jensen, A.T.R., Surface co-expression of two different PfEMP1 antigens on single Plasmodium falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1 (2010) PLoS Pathog, 6, pp. e1001083Kyes, S.A., Christodoulou, Z., Raza, A., Horrocks, P., Pinches, R., Rowe, J.A., Newbold, C.I., A well-conserved Plasmodium falciparum var gene shows 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Framing the application of Adaptation Pathways for agroforestry in Mediterranean drylands

Adaptation Pathways is a decision support tool designed to create adaptation policies under different climate change scenarios. This tool has been used successfully in several sectors and contexts such as coastal and river adaptation, urban heat waves, floods and rural livelihoods but its use in natural resource management, has faced several challenges and limitations. In the sector of agroforestry its use has seldom been done or documented and one of the reasons for this may due to some of its specific challenges. In this study, these challenges were addressed when using the Adaptation Pathways for the adaptation planning of three case studies in the semi-arid Alentejo region, a Mediterranean dryland of southern Portugal. This tool was integrated in a participatory approach combined with the Scenario Workshop method, to plan the adaptation of the agriculture and forestry sector of one municipality (Mértola) and two agroforestry farms (221 ha and 1000 ha). The methodology included, for each case study, 20 interviews, two workshops, literature review, expert analysis and the use of indicators of efficacy of adaptation measures, to define tipping points. The adaptation process and the resulting adaptation plans were evaluated by questionnaire and expert review. This combination of methods has supported the choice of effective adaptation measures for the case studies and when combined with several adaptation pathways and a landscape approach it supported the creation of integrated climate change adaptation plans that are now in implementation. We discuss how this combination of methods deals with limitation to Adaptation Pathways identified in the literature, conclude that the method was able to create adaptation plans that are now under implementation and present avenues for future research.info:eu-repo/semantics/publishedVersio

Amazonian Plant Natural Products: Perspectives For Discovery Of New Antimalarial Drug Leads

Plasmodium falciparum and P. vivax malaria parasites are now resistant, or showing signs of resistance, to most drugs used in therapy. Novel chemical entities that exhibit new mechanisms of antiplasmodial action are needed. New antimalarials that block transmission of Plasmodium spp. from humans to Anopheles mosquito vectors are key to malaria eradication efforts. Although P. vivax causes a considerable number of malaria cases, its importance has for long been neglected. Vivax malaria can cause severe manifestations and death; hence there is a need for P. vivax-directed research. Plants used in traditional medicine, namely Artemisia annua and Cinchona spp. are the sources of the antimalarial natural products artemisinin and quinine, respectively. Based on these compounds, semi-synthetic artemisinin-derivatives and synthetic quinoline antimalarials have been developed and are the most important drugs in the current therapeutic arsenal for combating malaria. In the Amazon region, where P. vivax predominates, there is a local tradition of using plant-derived preparations to treat malaria. Here, we review the current P. falciparum and P. vivax drug-sensitivity assays, focusing on challenges and perspectives of drug discovery for P. vivax, including tests against hypnozoites. We also present the latest findings of our group and others on the antiplasmodial and antimalarial chemical components from Amazonian plants that may be potential drug leads against malaria. © 2013 by the authors; licensee MDPI, Basel, Switzerland.18892199240A research agenda for malaria eradication: Drugs (2011) PLoS Med., 8, pp. e1000402. , malERA Consultative Group on DrugsWhite, N.J., Counter perspective: Artemisinin resistance: Facts, fears, and fables (2012) Am. J. Trop. Med. Hyg., 87, p. 785Phyo, A.P., Nkhoma, S., Stepniewska, K., Ashley, E.A., Nair, S., McGready, R., Ler Moo, C., Lwin, K.M., Emergence of artemisinin-resistant malaria on the western border of Thailand: A longitudinal study (2012) Lancet, 379, pp. 1960-1966Milliken, W., (1997) Plants for Malaria, Plants for Fever: Medicinal Species in Latin America, A Bibliographic Survey, p. 116. , Royal Botanic Gardens, Kew: Richmond, VA, USARuiz, L., Ruiz, L., Maco, M., Cobos, M., Gutierrez-Choquevilca, A.L., Roumy, V., Plants used by native Amazonian groups from the Nanay River (Peru) for the treatment of malaria (2011) J. Ethnopharmacol., 133, pp. 917-921Vigneron, M., Deparis, X., Deharo, E., Bourdy, G., Antimalarial remedies in French Guiana: A knowledge attitudes and practices study (2005) J. Ethnopharmacol., 98, pp. 351-360Bero, J., Quetin-Leclercq, J., Natural products published in 2009 from plants traditionally used to treat malaria (2011) Planta Med., 77, pp. 631-640Deharo, E., Ginsburg, H., Analysis of additivity and synergism in the anti-plasmodial effect of purified compounds from plant extracts (2011) Malar. J., 10 (SUPPL. 1), pp. S5Andrade-Neto, V.F., Brandao, M.G., Nogueira, F., Rosario, V.E., Krettli, A.U., Ampelozyziphus amazonicus Ducke (Rhamnaceae), a medicinal plant used to prevent malaria in the Amazon Region, hampers the development of Plasmodium berghei sporozoites (2008) Int. J. Parasitol., 38, pp. 1505-1511(2010) Global Report on Antimalarial Drug Efficacy and Drug Resistance: 2000-2010, p. 115. , World Health OrganizationWorld Health Organization: Geneva, SwitzerlandYoung, M.D., Moore, D.V., Chloroquine resistance in Plasmodium falciparum (1961) Am. J. Trop. Med. Hyg., 10, pp. 317-320Harinasuta, T., Migasen, S., Boonag, D., (1962) Chloroquine Resistance in Plasmodium Falciparum in Thailand, , UNESCO First Regional Symposium on Scientific Knowledge of Tropical Parasites: Singapore University, SingaporePeters, W., (1987) Chemotherapy and Drug Resistance in Malaria, , 2nd ed.Academic: London, UKRoper, C., Pearce, R., Nair, S., Sharp, B., Nosten, F., Anderson, T., Intercontinental spread of pyrimethamine-resistant malaria (2004) Science, 305, p. 1124Enserink, M., Combating malaria. Malaria treatment: ACT two (2007) Science, 318, pp. 560-563(2006) Guidelines for the Treatment of Malaria, p. 253. , World Health Organization. Roll Back Malaria Dept.World Health Organization: Geneva, SwitzerlandDa Mata, A.A., (2003) Flora Médica Brasiliense, , Valer Editora: Manaus, BrazilElisabetsky, E., Shanley, P., Ethnopharmacology in the Brazilian Amazon (1994) Pharmacol. Therap., 64, pp. 201-214Rodrigues, E., Plants and animals utilized as medicines in the Jau National Park (JNP), Brazilian Amazon (2006) Phytother. Res., 20, pp. 378-391Santos, J.F., Pagani, E., Ramos, J., Rodrigues, E., Observations on the therapeutic practices of riverine communities of the Unini River, AM, Brazil (2012) J. Ethnopharmacol., 142, pp. 503-515Suffredini, I.B., Paciencia, M.L., Varella, A.D., Younes, R.N., Antibacterial activity of Brazilian Amazon plant extracts (2006) Braz. J. Infect. Dis., 10, pp. 400-402Carneiro, A.L., Teixeira, M.F., Oliveira, V.M., Fernandes, O.C., Cauper, G.S., Pohlit, A.M., Screening of Amazonian plants from the Adolpho Ducke forest reserve, Manaus, state of Amazonas, Brazil, for antimicrobial activity (2008) Mem. Inst. Oswaldo Cruz, 103, pp. 31-38Pohlit, A.M., Lopes, N.P., Gama, R.A., Tadei, W.P., Neto, V.F., Patent literature on mosquito repellent inventions which contain plant essential oils-A review (2011) Planta Med., 77, pp. 598-617Pohlit, A.M., Rezende, A.R., Lopes Baldin, E.L., Lopes, N.P., Neto, V.F., Plant extracts, isolated phytochemicals, and plant-derived agents which are lethal to arthropod vectors of human tropical diseases-A review (2011) Planta Med., 77, pp. 618-630Schmidt, T.J., Khalid, S.A., Romanha, A.J., Alves, T.M., Biavatti, M.W., Brun, R., Da Costa, F.B., De Lacerda, M.V., The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases-part I (2012) Curr. Med. Chem., 19, pp. 2128-2175Achan, J., Talisuna, A.O., Erhart, A., Yeka, A., Tibenderana, J.K., Baliraine, F.N., Rosenthal, P.J., D'Alessandro, U., Quinine an old anti-malarial drug in a modern world: Role in the treatment of malaria (2011) Malar. J., 10, p. 144Bray, P.G., Ward, S.A., O'Neill, P.M., Quinolines and artemisinin: Chemistry, biology and history (2005) Curr. Top. Microbiol. Immunol., 295, pp. 3-38Pohlit, A.M., Jabor, V.A.P., Amorim, R.C.N., Costa Silva, E.E.C., Lopes, N.P., LC-ESI-MS determination of quassinoids Isobrucein B and neosergeolide in picrolemma sprucei stem infusions (2009) J. Braz. Chem. Soc., 20, pp. 1065-1070De Andrade-Neto, V.F., Pohlit, A.M., Pinto, A.C., Silva, E.C., Nogueira, K.L., Melo, M.R., Henrique, M.C., Costa, M.R., In vitro inhibition of plasmodium falciparum by substances isolated from Amazonian antimalarial plants (2007) Mem. Inst. Oswaldo Cruz, 102, pp. 359-365Pinto, A.C., Chaves, F.C., Dos Santos, P.A., Nunez, C.V., Tadei, W.P., Pohlit, A.M., Piper peltatum: Biomass and 4-nerolidylcatechol production (2010) Planta Med., 76, pp. 1473-1476Pinto, P.S., (2006) Estudo Químico e Atividade Biológica de Frações Do Extrato Etanólico da Raiz de Cassia Spruceana Benth. (Leguminosae: Caesalpinioideae), , M.Sc. Thesis, Universidade Federal do Amazonas, Manaus, BrazilHenrique, M.C., Nunomura, S.M., Pohlit, A.M., Indole alkaloids from the bark of Aspidosperma vargasii and A desmanthum (2010) Quim. Nova, 33, pp. 284-287Rocha Silva, E.L.F., Montoia, A., Amorim, R.C., Melo, M.R., Henrique, M.C., Nunomura, S.M., Costa, M.R., Dantas, G., Comparative in vitro and in vivo antimalarial activity of the indole alkaloids ellipticine, olivacine, cryptolepine and a synthetic cryptolepine analog (2012) Phytomed. Int. J. Phytother. Phytopharmacol., 20, pp. 71-76Dos Santos Torres, Z.E., Silveira, E.R., Rocha, E.S.L.F., Lima, E.S., De Vasconcellos, M.C., De Andrade Uchoa, D.E., Filho, R.B., Pohlit, A.M., Chemical composition of aspidosperma ulei markgr and antiplasmodial activity of selected indole alkaloids (2013) Molecules, 18, pp. 6281-6297Oliveira, A.B., Dolabela, M.F., Póvoa, M.M., Santos, C.A.M., Varotti, F.P., Antimalarial activity of ulein and proof of its action on the Plasmodium falciparum digestive vacuole (2010) Malar. 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