Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites

Chloroquine (CQ) is a cost effective antimalarial drug with a relatively good safety profile (or therapeutic index). However, CQ is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ-resistant strains, also reported for P. vivax. Despite CQ resistance, novel drug candidates based on the structure of CQ continue to be considered, as in the present work. One CQ analog was synthesized as monoquinoline (MAQ) and compared with a previously synthesized bisquinoline (BAQ), both tested against P. falciparum in vitro and against P. berghei in mice, then evaluated in vitro for their cytotoxicity and ability to inhibit hemozoin formation. Their interactions with residues present in the NADH binding site of P falciparum lactate dehydrogenase were evaluated using docking analysis software. Both compounds were active in the nanomolar range evaluated through the HRPII and hypoxanthine tests. MAQ and BAQ derivatives were not toxic, and both compounds significantly inhibited hemozoin formation, in a dose-dependent manner. MAQ had a higher selectivity index than BAQ and both compounds were weak PfLDH inhibitors, a result previously reported also for CQ. Taken together, the two CQ analogues represent promising molecules which seem to act in a crucial point for the parasite, inhibiting hemozoin formation.     

Heterogeneity of Putative Surface Layer Proteins in Lactobacillus helveticus

The S-layer-encoding genes of 21 Lactobacillus helveticus strains were characterized. Phylogenetic analysis based on the identified S-layer genes revealed two main clusters, one which includes a sequence similar to that of the slpH1 gene of L. helveticus CNRZ 892 and a second cluster which includes genes similar to that of prtY. These results were further confirmed by Southern blot hybridization. This study demonstrates S-layer gene variability in the species L. helveticus.     

Mathematical modeling of the ethanol fermentation of cashew apple juice by a flocculent yeast: the effect of initial substrate concentration and temperature

In this work, the effect of initial sugar concentration and temperature on the production of ethanol by Saccharomyces cerevisiae CCA008, a flocculent yeast, using cashew apple juice in a 1L-bioreactor was studied. The experimental results were used to develop a kinetic model relating biomass, ethanol production and total reducing sugar consumption. Monod, Andrews, Levenspiel and Ghose and Tyagi models were investigated to represent the specific growth rate without inhibition, with inhibition by substrate and with inhibition by product, respectively. Model validation was performed using a new set of experimental data obtained at 34 °C and using 100 g L⁻¹ of initial substrate concentration. The model proposed by Ghose and Tyagi was able to accurately describe the dynamics of ethanol production by S. cerevisiae CCA008 growing on cashew apple juice, containing an initial reducing sugar concentration ranging from 70 to 170 g L⁻¹ and temperature, from 26 to 42 °C. The model optimization was also accomplished based on the following parameters: percentage volume of ethanol per volume of solution (%V _ethanol/V _solution), efficiency and reaction productivity. The optimal operational conditions were determined using response surface graphs constructed with simulated data, reaching an efficiency and a productivity of 93.5% and 5.45 g L⁻¹ h⁻¹, respectively.

     

High fidelity: extra‐pair fertilisations in eight Charadrius plover species are not associated with parental relatedness or social mating system

Extra‐pair paternity is a common reproductive strategy in many bird species. However, it remains unclear why extra‐pair paternity occurs and why it varies among species and populations. Plovers (Charadrius spp.) exhibit considerable variation in reproductive behaviour and ecology, making them excellent models to investigate the evolution of social and genetic mating systems. We investigated inter‐ and intra‐specific patterns of extra‐pair parentage and evaluated three major hypotheses explaining extra‐pair paternity using a comparative approach based on the microsatellite genotypes of 2049 individuals from 510 plover families sampled from twelve populations that constituted eight species. Extra‐pair paternity rates were very low (0 to 4.1% of chicks per population). No evidence was found in support of the sexual conflict or genetic compatibility hypotheses, and there was no seasonal pattern of extra‐pair paternity (EPP). The low prevalence of EPP is consistent with a number of alternative hypotheses, including the parental investment hypothesis, which suggests that high contribution to care by males restricts female plovers from engaging in extra‐pair copulations. Further studies are needed to critically test the importance of this hypothesis for mate choice in plovers.     

The role of raw materials to achieve the Sustainable Development Goals: Tracing the risks and positive contributions of cobalt along the lithium-ion battery supply chain

Given the fast-growing demand for electric mobility, the European Union (EU) has invested in responsible sourcing of battery raw materials, but the sustainability of their value chains is not fully addressed. Life cycle sustainability assessment is a tool to identify social, economic, and environmental aspects of raw materials, but it is mostly used for negative impacts, whereas the supply and use of raw materials may also lead to benefits. The Sustainable Development Goals (SDGs) can help to determine how raw materials boost or hinder the achievement of a sustainable society. In this study, the SDGs were used as a reference to assess contributions and risks of cobalt supply for electric mobility in the EU and whether this technology supports the achievement of the SDGs. The risks were determined using eight indicators focused on social risks, but environmental aspects like water quality and usage, and greenhouse gas emissions were also considered. The literature and databases were consulted to identify which SDGs receive contributions or burdens. Global and European cobalt supply scenarios were defined, considering the most representative countries. Results indicate that, although some SDGs receive positive contributions, like SDG 8 (Decent work and economic growth) and SDG 13 (Climate action), most of the identified correlations are negative, especially for SDG 3 (Good health and well-being) and SDG 16 (Peace, justice, and strong institutions). The European scenario has a low risk toward socio-environmental issues in 53% of the assessed aspects, whereas the global scenario presents a high risk in 47% of them.     

Vertical distribution of coralline algae in the rocky intertidal of northern Chile

Studies on crustose corallines present in the intertidal region at three localities in northern Chile (30°S), show that these algae are well represented in exposed and protected sites, reaching up to 90% cover. Species composition differs between sites with the common occurrence of species or morphological variants of Spongites and a single taxon attributed to Phymatolithon at the most exposed sites, and species of Lithophyllum and Titanoderma at more protected localities. The two Lithophyllum taxa recorded are distinguished by the presence/absence of protuberances, cell size and degree of calcification, while Titanoderma taxa are segregated by the thickness of the thallus, hypothallic and perithallic cell size and shape. Spongites taxa are distinguished on the basis of external morphology and anatomical features such as cell size, degree of calcification and percentage of fusions between cells. The variability of these features within each species is still unknown thus, the taxa remain without specific epithet until further studies. Examination of specific types recorded for nearby regions are also required in order to clarify the taxonomy of the group in these coasts.     

Characterization and prevalence of pigments in the muscle of hawkfish (Cheilodactylus bergi)

Melanin pigment was prevalent in skeletal muscle of 338 out of 1079 Cheilodactylus bergi sampled from the Argentine-Uruguay Common Fisheries Zone. A higher proportion of males than of females was pigmented, and only in males did that proportion increase with body length. No parasites were found in the muscle.     

LTD4 induces hyperresponsiveness to histamine in bovine airway smooth muscle: role of SR-ATPase Ca2+ pump and tyrosine kinase

Airway hyperresponsiveness is a key feature of asthma, but its mechanisms remain poorly understood. Leukotriene D(4) (LTD(4)) is one of the few molecules capable of producing airway hyperresponsiveness. In this study, LTD(4), but not leukotriene C(4) (LTC(4)), produced a leftward displacement of the concentration-response curve to histamine in bovine airway smooth muscle strips. Neither LTC(4) nor LTD(4) modified the concentration-response curve to carbachol. In simultaneous measurements of intracellular Ca(2+) ([Ca(2+)](i)) and contraction, histamine or carbachol produced a transient Ca(2+) peak followed by a plateau, along with a contraction. LTD(4) increased the histamine-induced transient Ca(2+) peak and contraction but did not modify responses to carbachol. Enhanced responses to histamine induced by LTD(4) were not modified by staurosporine or chelerythrine but were abolished by genistein. Western blot showed that carbachol, but not histamine, caused intense phosphorylation of extracellular signal-regulated kinase 1/2 and that LTD(4) significantly enhanced the phosphorylation induced by histamine, but not by carbachol. L-type Ca(2+) channel participation in the hyperresponsiveness to histamine was discarded because LTD(4) did not modify the [Ca(2+)](i) changes induced by KCl. In tracheal myocytes, LTD(4) enhanced the transient Ca(2+) peak induced by histamine (but not by carbachol) and the sarcoplasmic reticulum (SR) Ca(2+) refilling. Genistein abolished this last LTD(4) effect. Partial blockade of the SR-ATPase Ca(2+) pump with cyclopiazonic acid reduced the Ca(2+) transient peak induced by histamine but not by carbachol. These results suggested that LTD(4) induces hyperresponsiveness to histamine through activation of the tyrosine kinase pathway and an increasing SR-ATPase Ca(2+) pump activity. L-type Ca(2+) channels seemed not to be involved in this phenomenon.