This paper provides an overview of stable isotope analysis (H, C, N, O, Si) of the macroand microscopic remains from aquatic organisms found in lake sediment records and their application in (palaeo)environmental science. Aquatic organisms, including diatoms, macrophytes, invertebrates, and fish, can produce sufficiently robust remains that preserve well as fossils and can be identified in lake sediment records. Stable isotope analyses of these remains can then provide valuable insights into habitat-specific biogeochemistry, feeding ecology, but also on climatic and hydrological changes in and around lakes. Since these analyses focus on the remains of known and identified organisms, they can provide more specific and detailed information on past ecosystem, food web and environmental changes affecting different compartments of lake ecosystems than analyses on bulk sedimentary organic matter or carbonate samples. We review applications of these types of analyses in palaeoclimatology, palaeohydrology, and palaeoecology. Interpretation of the environmental 'signal' provided by taxon-specific stable isotope analysis requires a thorough understanding of the ecology and phenology of the organism groups involved. Growth, metabolism, diet, feeding strategy, migration, taphonomy and several other processes can lead to isotope fractionation or otherwise influence the stable isotope signatures of the remains from aquatic organisms. This paper includes a review of the (modern) calibration, culturing and modeling studies used to quantify the extent to which these factors influence stable isotope values and provides an outlook for future research and methodological developments for the different examined fossil groups.

Apicomplexan infections cause substantial morbidity and mortality, worldwide. New, improved therapies are needed. Herein, we create a next generation anti-apicomplexan lead compound, JAG21, a tetrahydroquinolone, with increased sp3-character to improve parasite selectivity. Relative to other cytochrome b inhibitors, JAG21 has improved solubility and ADMET properties, without need for pro-drug. JAG21 significantly reduces Toxoplasma gondii tachyzoites and encysted bradyzoites in vitro, and in primary and established chronic murine infections. Moreover, JAG21 treatment leads to 100% survival. Further, JAG21 is efficacious against drug-resistant Plasmodium falciparum in vitro. Causal prophylaxis and radical cure are achieved after P. berghei sporozoite infection with oral administration of a single dose (2.5 mg/kg) or 3 days treatment at reduced dose (0.625 mg/kg/day), eliminating parasitemia, and leading to 100% survival. Enzymatic, binding, and co-crystallography/pharmacophore studies demonstrate selectivity for apicomplexan relative to mammalian enzymes. JAG21 has significant promise as a pre-clinical candidate for prevention, treatment, and cure of toxoplasmosis and malaria.

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22Stable isotope analyses of ostracod shells are a commonly-used proxy for 23 palaeoenvironmental reconstruction. Although the fundamental controls on isotope 24 composition of ostracod shells are well understood and, in some instances, quantifiable, the 25 paleoclimatic and palaeoenvironmental interpretation of records from lake sediments depends 26 strongly on the characteristics of individual lakes including the climatic setting, depth, volume, 27 hydrology, aquatic vegetation and catchment properties. This is particularly important for 28 coastal lakes where physio-chemical variations may occur on diurnal timescales. Here, we 29 combine variations in δ 18 O water , δ 18 O ostracod and δ 13 C ostracod , hourly water temperature, and 30 Mg/Ca ostracod inferred water temperatures (constraining calcification temperature) to improve 31 palaeoenvironmental interpretation and provide insights into lake carbon cycle. The dataset 32 improves understanding of complex coastal lake site systematics and downcore interpretation 33 of stable isotopes from C. torosa, a geographically widespread brackish water ostracod. The 34 δ 18 O ostracod values show a complex relationship with temperature and suggest, in most 35 circumstances, that δ 18 O water is the dominant control on δ 18 O ostracod . During times of fresher 36 water, δ 13 C ostracod increases, suggesting increasing aquatic productivity. Above a certain 37 δ 18 O water threshold however, aquatic productivity begins to decline. The interpretation of 38 δ 13 C ostracod in some coastal lakes, may therefore be dependent on understanding of the range 39 of expected δ 18 O water . Due to short-term (diurnal to seasonal) variations that cause large 2 40 ranges in δ 18 O water and δ 18 O ostracod , stable isotope analyses of C. torosa should be: 1) 41 undertaken on multiple single shells 2) where carapaces are preserved, paired with trace-42 element/Ca analyses on the same individual; and 3) undertaken alongside a study of the 43 modern lake system.