Synthesis and biological evaluation of anti-Toxoplasma gondii activity of a novel scaffold of thiazolidinone derivatives

We designed and synthesised novel N-substituted 1,3-thiazolidin-4-one derivatives for the evaluation of their anti-Toxoplasma gondii efficacy. This scaffold was functionalised both at the N1-hydrazine portion with three structurally different moieties and at the lactam nitrogen with substituted benzyl groups selected on the basis of our previous structure-activity relationships studies. Using three different assay methods, the compounds were assessed in vitro to determine both the levels of efficacy against the tachyzoites of T. gondii (IC₅₀?=?5–148?μM), as well as any evidence of cytotoxicity towards human host cells (TD₅₀?=?68 to ≥320?μM). Results revealed that ferrocene-based thiazolidinones can possess potent anti-tachyzoite activity (TI =2–64).     

Genotoxicity of cigarette smoking in maternal and newborn lymphocytes

Tobacco smoke contains a large number of substances known to induce DNA damage and to be hazardous to human health. Several reviews and meta-analyses have reported an association between maternal or paternal smoking habits and genetic-related diseases, such as cancer, in children. The aim of the present study was to evaluate the level of DNA damage in lymphocytes of active- and passive-smoking mothers and in their newborns, using the comet assay. A total of 40 active smokers, 40 passive smokers, and 40 non-smokers, and their respective newborns, were evaluated. The active smokers presented a statistically significant increase of DNA damage when compared to the non-smokers and passive-smokers. No significant difference was observed between passive and non-smoking women. Similar results were detected in newborns. Those born to active-smoking mothers presented higher levels of DNA damage than those from passive- and non-smoking mothers. Additionally, no significant difference was detected between newborns from non-smoking and passive-smoking mothers. Also, no statistically significant difference in DNA damage was observed between mothers and their respective newborns, and a positive correlation in the level of DNA damage was detected between them. Logistic regression analyses showed positive associations between DNA damage, spontaneous abortion and smoking status. In conclusion, our data indicate that tobacco exposure during pregnancy has genotoxic effects for both mother and child, and it can be considered an important risk factor for childhood cancer or other genetic-related diseases.     

Biogeography of microbial communities in high-latitude ecosystems: Contrasting drivers for methanogens,methanotrophs and global prokaryotes

Methane-cycling is becoming more important in high-latitude ecosystems as global warming makes permafrost organic carbon increasingly available. We explored 387 samples from three high-latitudes regions (Siberia, Alaska and Patagonia) focusing on mineral/organic soils (wetlands, peatlands, forest), lake/pond sediment and water. Physicochemical, climatic and geographic variables were integrated with 16S rDNA amplicon sequences to determine the structure of the overall microbial communities and of specific methanogenic and methanotrophic guilds. Physicochemistry (especially pH) explained the largest proportion of variation in guild composition, confirming species sorting (i.e., environmental filtering) as a key mechanism in microbial assembly. Geographic distance impacted more strongly beta diversity for (i) methanogens and methanotrophs than the overall prokaryotes and, (ii) the sediment habitat, suggesting that dispersal limitation contributed to shape the communities of methane-cycling microorganisms. Bioindicator taxa characterising different ecological niches (i.e., specific combinations of geographic, climatic and physicochemical variables) were identified, highlighting the importance of Methanoregula as generalist methanogens. Methylocystis and Methylocapsa were key methanotrophs in low pH niches while Methylobacter and Methylomonadaceae in neutral environments. This work gives insight into the present and projected distribution of methane-cycling microbes at high latitudes under climate change predictions, which is crucial for constraining their impact on greenhouse gas budgets.     

Comparative biochemical studies of isozymes of isocitrate dehydrogenase from the mouse

Summary Biochemical properties of cytoplasmic and mitochondrial isozymes of isocitrate dehydrogenase from DBA/2J mice were compared under various experimental conditions. These included K_m determinations, coenzyme specificity, pH dependence, urea, iodoacetate and thermal inactivation and fluorescence titration studies. From these comparative studies each isozyme was found to have distinct coenzyme specificity, thermal stability and sensitivity to alkylation. In the case of the cytoplasmic isozyme, both NADP⁺ and isocitrate protect the enzyme against thermal denaturation but not iodoacetate inactivation. On the contrary, neither NADP⁺ nor isocitrate protects the mitochondrial enzyme against thermal or iodoacetate inactivation. Both isozymes exhibit similar fluorescence properties. NADP⁺ and NADPH, but not isocitrate, cause quenching of protein fluorescence. Enhancement of coenzyme fluorescence and protein energy transfer was observed when either isozyme was added to NADPH solutions. Further addition of isocitrate or isocitrate-Mg⁺⁺ to a NADPH-enzyme solution caused a decrease of the enhancement of coenzyme fluorescence and protein energy transfer, but not quenching of protein fluorescence, indicating the formation of a ternary complex. This observation precludes the mechanism of mutual exclusion between NADPH and isocitrate in the active site of the enzyme.Abbreviations used IDH isocitrate dehydrogenase - NHDP⁺ nicotinamide-hypoxanthine dinucleotide phosphate - TNADP⁺ thionicotinamide-adenine dinucoleotide phosphate - AcPyADP⁺ 3-acetylpyridine-adenine dinucleotide phosphate NIH Visiting Fellow.     

Alterations in cytokines and haematological parameters during the acute and convalescent phases of Plasmodium falciparum and Plasmodium vivax infections

Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL)-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF)-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.     

Protective Effects of Inosine on Memory Consolidation in a Rat Model of Scopolamine-Induced Cognitive Impairment: Involvement of Cholinergic Signaling,Redox Status,and Ion Pump Activities

Neurochemical Research - This study investigated the effects of inosine on memory acquisition and consolidation, cholinesterases activities, redox status and Na+, K+-ATPase activity in a rat model...     

Propagation of the loud “tchó” call of golden-backed uakaris, Cacajao melanocephalus, in the black-swamp forests of the upper Amazon

Arboreal primates use loud vocalisations to transmit information in densely vegetated habitats. These vocalisations are likely to show adaptations to increase their propagation and to transmit information. Golden-backed uakaris, Cacajao melanocephalus, emit a loud vocalization termed the “tchó” call, which seems to function as a contact call and encodes information on the individual signaler and behavioural context. Because the call is often used for communication over relatively large distances, we were interested in its propagation in the wild. The aim of the present study was to investigate the degradation patterns of the tchó call in the flooded igapó forest. We examined via playback experiments how the acoustic parameters of this call changed with increasing distance from the playback speaker. We broadcast 12 tchó calls and rerecorded them along a transect at distances of 10, 20, 40, 80 and 160?m from the speaker in two igapó forest patches in Jaú National Park, Amazonas, Brazil. At 160?m from the speaker, the tchó call degraded in both patches and was barely recordable. Up to a distance of 80?m, the bandwidth and number of harmonics in the call decreased with increasing distance, while the lowest frequency increased. The highest frequency (HF) did not gradually decrease with increasing distance. However, when we compared the HF at distances of 10 and 80?m, we could see a clear decrease in this parameter. Call duration increased compared with the broadcast signal up to 40?m because of reverberation, but decreased at 80?m as the weaker echoes of the call attenuated. These changes may reveal information about the signaler’s distance during signal transmission. The frequency of maximum energy (FME) of the tchó call decreased significantly when comparing recordings made at 10 and 80?m. Nevertheless, it did not show a consistent and gradual decrease with increasing rerecording distance (at least up to 80?m). FME remained relatively stable (±50?Hz on average, at least up to 80?m) when compared to the other call parameters, suggesting that the tchó call may be adapted to transmit information with some efficiency throughout the igapó forest.     

Unraveling interactions: do temperature and competition with native species affect the performance of the non-indigenous sun coral Tubastraea coccinea?

Coral Reefs - The impact of invasive species has been increasing in recent decades due to globalization, threatening marine biodiversity. Tubastraea spp. (sun corals) have been spreading worldwide,...     

Molecular characterization of a novel pathogen-responsive receptor kinase-like in <Emphasis Type="Italic">Citrus limon</Emphasis>

Infection by pathogenic microorganisms is a source of biological stress in plants. Understanding the interaction between plants and microbial infection at molecular level might contribute to our understanding for the effective control of the disease. Here, we isolated a novel putative receptor kinase-like protein (Citrus limon P5) that is the first Lec-receptor kinase-like protein isolated in lemon during a pathogen infection. C. limon P5 cDNA fragment was detected by differential display assay in C. limon during Capnodium citri (sooty mold) infection. The deduced amino acid sequence of P5 full-length cDNA revealed a 83% sequence homology with a receptor kinase-like protein from Arabidopsis thaliana characterized by a N-terminal lectin domain and C-terminal serine/threonine conserved domain. The inhibition of the pathogen-responsive P5 by the protein kinase inhibitor staurosporine and by a mitogen-activated protein kinase inhibitor (PD 98059) indicated a defense mechanism in C. limon against pathogens mediated via signal transduction pathway. To our knowledge, this is the first evidence that C. limon uses this putative defense mechanism against pathogens. The role of this protein is discussed as a starting point to understanding the molecular mechanisms in the C. limon in response to C. citri infection.