ABSTRACT
Historical ecology has revolutionized our understanding of fisheries and cultural landscapes, demonstrating the value of historical data for evaluating the past, present, and future of Earth's ecosystems. Despite several important studies, Indigenous fisheries generally receive less attention from scholars and managers than the 17th-20th century capitalist commercial fisheries that decimated many keystone species, including oysters. We investigate Indigenous oyster harvest through time in North America and Australia, placing these data in the context of sea level histories and historical catch records. Indigenous oyster fisheries were pervasive across space and through time, persisting for 5000-10,000 years or more. Oysters were likely managed and sometimes "farmed," and are woven into broader cultural, ritual, and social traditions. Effective stewardship of oyster reefs and other marine fisheries around the world must center Indigenous histories and include Indigenous community members to co-develop more inclusive, just, and successful strategies for restoration, harvest, and management.
Subject(s)
Fisheries , Ostreidae , Animals , Ecology , Ecosystem , SeafoodABSTRACT
The purine nucleoside 5'-deoxy-5'-(hydroxyethylthio)-adenosine (HETA) is an analog of the polyamine pathway metabolite 5'-deoxy-5'-(methylthio)-adenosine (MTA). HETA is a lead structure for the ongoing development of selectively targeted trypanocidal agents. Thirteen novel HETA analogs were synthesized and examined for their in vitro trypanocidal activities against bloodstream forms of Trypanosoma brucei brucei LAB 110 EATRO and at least one drug-resistant Trypanosoma brucei rhodesiense clinical isolate. New compounds were also assessed in a cell-free assay for their activities as substrates of trypanosome MTA phosphorylase. The most potent analog in this group was 5'-deoxy-5'-(hydroxyethylthio)-tubercidin, whose in vitro cytotoxicity (50% inhibitory concentration [IC50], 10 nM) is 45 times greater than that of HETA (IC50, 450 nM) against pentamidine-resistant clinical isolate KETRI 269. Structure-activity analyses indicate that the enzymatic cleavage of HETA analogs by trypanosome MTA phosphorylase is not an absolute requirement for trypanocidal activity. This suggests that additional biochemical mechanisms are associated with the trypanocidal effects of HETA and its analogs.
Subject(s)
Deoxyadenosines/chemistry , Thionucleosides/chemistry , Trypanocidal Agents , Trypanosoma brucei brucei/drug effects , Trypanosoma brucei rhodesiense/drug effects , Tubercidin/analogs & derivatives , Tubercidin/pharmacology , Animals , Deoxyadenosines/chemical synthesis , Deoxyadenosines/pharmacology , Dose-Response Relationship, Drug , Drug Resistance , Inhibitory Concentration 50 , Parasitic Sensitivity Tests , Purine-Nucleoside Phosphorylase/metabolism , Substrate Specificity , Thionucleosides/chemical synthesis , Thionucleosides/pharmacology , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacology , Trypanosoma brucei brucei/enzymology , Trypanosoma brucei brucei/growth & development , Trypanosoma brucei rhodesiense/enzymology , Trypanosoma brucei rhodesiense/growth & development , Tubercidin/chemical synthesis , Tubercidin/chemistryABSTRACT
6-Methylpurine-beta-D-riboside (beta-D-MPR) has been synthesized by coupling 6-methylpurine and 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribose using conditions that produce the beta-D-anomer exclusively. The in vitro antitumor effects of beta-D-MPR and 6-methyl-purine-alpha-D-riboside (alpha-D-MPR) in five human tumor cell lines showed that beta-D-MPR was highly active (IC(50) values ranging from 6 to 34 nM). alpha-D-MPR, although less active than beta-D-MPR, also exhibited significant antitumor effects (IC50 values ranging from 1.47 to 4.83 microM).
