Warm temperature acclimation impacts metabolism of paralytic shellfish toxins from Alexandrium minutum in commercial oysters

© 2015 John Wiley & Sons Ltd. Species of Alexandrium produce potent neurotoxins termed paralytic shellfish toxins and are expanding their ranges worldwide, concurrent with increases in sea surface temperature. The metabolism of molluscs is temperature dependent, and increases in ocean temperature may influence both the abundance and distribution of Alexandrium and the dynamics of toxin uptake and depuration in shellfish. Here, we conducted a large-scale study of the effect of temperature on the uptake and depuration of paralytic shellfish toxins in three commercial oysters (Saccostrea glomerata and diploid and triploid Crassostrea gigas, n = 252 per species/ploidy level). Oysters were acclimated to two constant temperatures, reflecting current and predicted climate scenarios (22 and 27 °C), and fed a diet including the paralytic shellfish toxin-producing species Alexandrium minutum. While the oysters fed on A. minutum in similar quantities, concentrations of the toxin analogue GTX1,4 were significantly lower in warm-acclimated S. glomerata and diploid C. gigas after 12 days. Following exposure to A. minutum, toxicity of triploid C. gigas was not affected by temperature. Generally, detoxification rates were reduced in warm-acclimated oysters. The routine metabolism of the oysters was not affected by the toxins, but a significant effect was found at a cellular level in diploid C. gigas. The increasing incidences of Alexandrium blooms worldwide are a challenge for shellfish food safety regulation. Our findings indicate that rising ocean temperatures may reduce paralytic shellfish toxin accumulation in two of the three oyster types; however, they may persist for longer periods in oyster tissue

Benzyl- and dibenzyl tetrahydropyridinylidene ammonium salts with antiplasmodial and antitrypanosomal activity

Several 1-benzyl and 1,3-dibenzyl derivatives of tetrahydropyridinylidene salts with differing electron withdrawing substituents at the aromatic residues have been prepared. In addition, the amine moiety in position 4 was varied. The new compounds were investigated for their antiplasmodial and antitrypanosomal activities as well as for their cytotoxicity. They were characterized using FT-IR, HRMS and NMR spectroscopy. Structure-activity relationships including reported compounds are discussed. Graphical abstract: [Figure not available: see fulltext.]. © 2022, The Author(s)

Morphological differences between habitats are associated with physiological and behavioural trade-offs in stickleback (Gasterosteus aculeatus)

F.S. and A.J.W.W. were supported by the Australian Research Council, M.M.W. was supported by The University of St Andrews and R.S.J. and J.T. were supported by Coventry UniversityLocal specialization can be advantageous for individuals and may increase the resilience of the species to environmental change. However, there may be trade-offs between morphological responses and physiological performance and behaviour. Our aim was to test whether habitat-specific morphology of stickleback (Gasterosteus aculeatus) interacts with physiological performance and behaviour at different salinities. We rejected the hypothesis that deeper body shape of fish from habitats with high predation pressure led to decreases in locomotor performance. However, there was a trade-off between deeper body shape and muscle quality. Muscle of deeper-bodied fish produced less force than that of shallow-bodied saltmarsh fish. Nonetheless, saltmarsh fish had lower swimming performance, presumably because of lower muscle mass overall coupled with smaller caudal peduncles and larger heads. Saltmarsh fish performed better in saline water (20 ppt) relative to freshwater and relative to fish from freshwater habitats. However, exposure to salinity affected shoaling behaviour of fish from all habitats and shoals moved faster and closer together compared with freshwater. We show that habitat modification can alter phenotypes of native species, but local morphological specialization is associated with trade-offs that may reduce its benefits.Publisher PDFPeer reviewe

8-amino-6-methoxyquinoline-tetrazole hybrids: Impact of linkers on antiplasmodial activity

A new series of compounds was prepared from 6-methoxyquinolin-8-amine or its N-(2-aminoethyl) analogue via Ugi-azide reaction. Their linkers between the quinoline and the tert-butyltetrazole moieties differ in chain length, basicity and substitution. Compounds were tested for their antiplasmodial activity against Plasmodium falciparum NF54 as well as their cytotoxicity against L-6-cells. The activity and the cytotoxicity were strongly influenced by the linker and its substitution. The most active compounds showed good activity and promising selectivity

Synthesis and antiprotozoal activity of azabicyclo-nonane pyrimidine hybrids

2,4-Diaminopyrimidines and (dialkylamino)azabicyclo-nonanes possess activity against protozoan parasites. A series of fused hybrids were synthesized and tested in vitro against pathogens of malaria tropica and sleeping sickness. The activities and selectivities of compounds strongly depended on the substitution pattern of both ring systems as well as on the position of the nitrogen atom in the bicycles. The most promising hybrids of 3-azabicyclo-nonane with 2-aminopyrimidine showed activity against P. falciparum NF54 in submicromolar concentration and high selectivity. A hybrid with pyrrolidino substitution of the 2-azabicyclo-nonane as well as of the pyrimidine moiety exhibited promising activity against the multiresistant K1 strain of P. falciparum. A couple of hybrids of 2-azabicyclo-nonanes with 2-(dialkylamino)pyrimidines possessed high activity against Trypanosoma brucei rhodesiense STIB900 and good selectivity

Antarctic fish can compensate for rising temperatures: Thermal acclimation of cardiac performance in Pagothenia borchgrevinki

Antarctic fish Pagothenia borchgrevinki in McMurdo Sound, Antarctica, inhabit one of the coldest and most thermally stable of all environments. Sea temperatures under the sea ice in this region remain a fairly constant -1.86 degrees C year round. This study examined the thermal plasticity of cardiac function in P. borchgrevinki to determine whether specialisation to stable low temperatures has led to the loss of the ability to acclimate physiological function. Fish were acclimated to - 1 degrees C and 4 degrees C for 4 - 5 weeks and cardiac output was measured at rest and after exhaustive exercise in fish acutely transferred from their acclimation temperature to - 1, 2, 4, 6 and 8 degrees C. In the - 1 degrees C acclimated fish, the factorial scope for cardiac output was greatest at - 1 degrees C and decreased with increasing temperature. Increases in cardiac output with exercise in the - 1 degrees C acclimated fish was achieved by increases in both heart rate and stroke volume. With acclimation to 4 degrees C, resting cardiac output was thermally independent across the test temperatures; furthermore, factorial scope for cardiac output was maintained at 4, 6 and 8 degrees C, demonstrating thermal compensation of cardiac function at the higher temperatures. This was at the expense of cardiac function at - 1 degrees C, where there was a significant decrease in factorial scope for cardiac output in the 4 degrees C acclimated fish. Increases in cardiac output with exercise in the 4 degrees C acclimated fish at the higher temperatures was achieved by changes in heart rate alone, with stroke volume not varying between rest and exercise. The thermal compensation of cardiac function in P. borchgrevinki at higher temperatures was the result of a change in pumping strategy from a mixed inotropic/chronotropic modulated heart in - 1 degrees C acclimated fish at low temperatures to a purely chronotropic modulated heart in the 4 degrees C acclimated fish at higher temperatures. In spite of living in a highly stenothermal cold environment, P. borchgrevinki demonstrated the capacity to thermally acclimate cardiac function to elevated temperatures, thereby allowing the maintenance of factorial scope and the support of aerobic swimming at higher temperatures

New acyl derivatives of 3-aminofurazanes and their antiplasmodial activities

An N-acylated furazan-3-amine of a Medicines for Malaria Venture (MMV) project has shown activity against different strains of Plasmodium falciparum. Seventeen new derivatives were prepared and tested in vitro for their activities against blood stages of two strains of Plasmodium falciparum. Several structure-activity relationships were revealed. The activity strongly depended on the nature of the acyl moiety. Only benzamides showed promising activity. The substitution pattern of their phenyl ring affected the activity and the cytotoxicity of compounds. In addition, physicochemical parameters were calculated (log P, log D, ligand efficiency) or determined experimentally (permeability) via a PAMPA. The N-(4-(3,4-diethoxyphenyl)-1,2,5-oxadiazol-3-yl)-3-(trifluoromethyl)benzamide possessed good physicochemical properties and showed high antiplasmodial activity against a chloroquine-sensitive strain (IC50(NF54) = 0.019 microM) and even higher antiplasmodial activity against a multiresistant strain (IC50(K1) = 0.007 microM). Compared to the MMV compound, the permeability and the activity against the multiresistant strain were improved

New derivatives of the multi-stage active Malaria Box compound MMV030666 and their antiplasmodial potencies

MMV's Malaria Box compound MMV030666 shows multi-stage activity against various strains of Plasmodium falciparum and lacks resistance development. To evaluate the importance of its diarylether partial structure, diarylthioethers and diphenylamines with varying substitution patterns were prepared. A number of evident structure-activity relationships were revealed. Physicochemical and pharmacokinetic parameters were determined experimentally (passive permeability) or calculated. Compared to the lead compound a diarylthioether was more active and less cytotoxic resulting in an excellent selectivity index of 850. In addition, pharmacokinetic and physicochemical parameters were improved

New 2‑aminopyrimidine derivatives and their antitrypanosomal and antiplasmodial activities

Novel 2-aminopyrimidine derivatives were prepared from acyclic starting materials, benzylidene acetones and ammonium thiocyanates, via 5 steps, including ring closure, aromatization, S-methylation, oxidation to methylsulfonyl compounds, and formation of guanidines with suitable amines. The prepared compounds differ from each other by the substitutions of their amino group and of their phenyl ring. The 2-aminopyrimidines were tested by use of microplate assays for their in vitro activities against a causative organism of sleeping sickness, Trypanosoma brucei rhodesiense, as well as against a causative organism of malaria, Plasmodium falciparum NF54. Their cytotoxic properties were determined with L-6 cells (rat skeletal myoblasts). Some of the compounds exhibited quite good antitrypanosomal activity, and others showed excellent antiplasmodial activity. The influence of the structural modifications on these activities is discussed

Antiprotozoal activity of azabicyclo-nonanes linked to tetrazole or sulfonamide cores

N-(Aminoalkyl)azabicyclo[3.2.2]nonanes possess antiplasmodial and antitrypanosomal activity. A series with terminal tetrazole or sulfonamido partial structure was prepared. The structures of all new compounds were confirmed by NMR and IR spectroscopy and by mass spectral data. A single crystal structure analysis enabled the distinction between isomers. The antiprotozoal activities were examined in vitro against strains of Plasmodium falciparum and Trypanosoma brucei rhodesiense (STIB 900). The most active sulfonamide and tetrazole derivates showed activities in the submicromolar range