Neurotrophic Effects of Extracellular Guanosine

Central nervous system (CNS) astrocytes release guanosine extracellularly, that exerts trophic effects. In CNS, extracellular guanosine (GUO) stimulates mitosis, synthesis of trophic factors, and cell differentiation, including neuritogenesis, is neuroprotective, and reduces apoptosis due to several stimuli. Specific receptor-like binding sites for eGUO in the nervous system may mediate its effects through both MAP kinase and PI3-kinase signalling pathways. Extracellular guanine (eGUA) also exerts several effects; the trophic effects of eGUO are likely regulated by conversion of eGUO to eGUA by a membrane located purine nucleoside phosphorylase (ecto-PNP) and by conversion of eGUA to xanthine by guanine deaminase.     

Resistance of the AF-28 sorghum variety to Contarinia sorghicola

The variety AF-28 of Sorghum bicolor Pers and the hybrid R-1090 were compared in relation to the sorghum midge, Contarinia sorghicola (Coquillet), (Diptera: Cecidomyidae) in two counties of the State of São Paulo. They were compared in seven successive monthly trials beginning in September 1972. Averages of 252 and 137 adult flies emerged per head of the hybrid R-1090 in Campinas and Jaboticabal respectively, while 2.9 and 0.8 emerged from AF-28. The damage was graded with a visual scale from 0 to 4. Average damage grades of 3.5 and 3.3 were attributed to the hybrid R-1090 in Campinas and Jaboticabal respectively, while the variety AF-28 had averages of 0.5 and 0.3, respectively.

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Résumé La variété AF-28 et l'hybride R-1090 de Sorghum bicolor Pers. ont été comparés à différentes époques de l'année et en deux localités différentes de l'Etat de Sâo Paulo, Brésil.On n'a pas constaté d'interaction variété x époque ou variété x lieu.AF-28 a prouvé sa résistance à toutes les époques, aussi bien dans un lieu que dans l'autre; l'hybride par contre s'est montré grandement susceptible.Des moyennes de 252,2 et 136,7 mouches par panicule ont été observées pour l'hybride R-1090 à Campinas et à Jaboticabal contre 2,9 et 0,8 seulement par panicule de AF-28. Le préjudice a été estimé visuellement selon une échelle de 0 à 4. Des préjudices d'une valeur moyenne de 3,5 et 3,3 ont été attribués à l'hybride R-1090 à Campinas et à Jaboticabal respectivement, alors que simultanément la variété AF-28 ne subissait que des préjudices évalués à 0,5 et 0,3 respectivement.Quatre espèces de microhyménoptères parasites de Contarinia sorghicola ont été récoltées au cours de ce travail: Eupelmus popa et trois espèces différentes du genre Tetrastichus.

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Part of a thesis presented to the School of Sciences of Bauru for fulfilment of the requirement for the degree of Doctor of Science. This research was financed by the Project 72/1471 of the agreement UNIÃO-ESTADO-FAPESP and by CNPq Project 12910/73.     

Chromatin modifiers and recombination factors promote a telomere fold-back structure,that is lost during replicative senescence

Telomeres have the ability to adopt a lariat conformation and hence, engage in long and short distance intra-chromosome interactions. Budding yeast telomeres were proposed to fold back into subtelomeric regions, but a robust assay to quantitatively characterize this structure has been lacking. Therefore, it is not well understood how the interactions between telomeres and non-telomeric regions are established and regulated. We employ a telomere chromosome conformation capture (Telo-3C) approach to directly analyze telomere folding and its maintenance in S. cerevisiae. We identify the histone modifiers Sir2, Sin3 and Set2 as critical regulators for telomere folding, which suggests that a distinct telomeric chromatin environment is a major requirement for the folding of yeast telomeres. We demonstrate that telomeres are not folded when cells enter replicative senescence, which occurs independently of short telomere length. Indeed, Sir2, Sin3 and Set2 protein levels are decreased during senescence and their absence may thereby prevent telomere folding. Additionally, we show that the homologous recombination machinery, including the Rad51 and Rad52 proteins, as well as the checkpoint component Rad53 are essential for establishing the telomere fold-back structure. This study outlines a method to interrogate telomere-subtelomere interactions at a single unmodified yeast telomere. Using this method, we provide insights into how the spatial arrangement of the chromosome end structure is established and demonstrate that telomere folding is compromised throughout replicative senescence.     

Impact of brood parasitism and predation on nest survival of the fan-tailed gerygone in New Caledonia

Predation and brood parasitism are common reasons for nesting failure in passerine species and the additive impact by invasive species is a major conservation concern, particularly on tropical islands. Recognising the relative contribution of the different components of nesting failure rates is important to understand co-evolutionary interactions within brood parasite–host systems. In the remote archipelago of New Caledonia, the fan-tailed gerygone Gerygone flavolateralis is the exclusive host of the brood-parasitic shining bronze-cuckoo Chalcites lucidus. Additionally, invasive rodents also possibly have an impact on breeding success. To estimate the impact of potential nest predators, we 1) video monitored nests to identify predators, 2) estimated the probability of predation based on nest visibility and predator abundance and 3) tested the possibility that the location of experimental nests and lack of odour cues decrease the predation by rodents. In addition, we estimated nest survival rates using data collected in different habitats over the course of eight breeding seasons. Nesting success of fan-tailed gerygones was relatively low and predation was the main cause of nesting failure. We recorded mainly predation by native birds, including the shining bronze-cuckoo, whereas predation by rats was rare. In open habitats predation by cuckoos was much lower than predation by other avian predators. Neither predator activity around nests nor nest visibility influenced the probability of predation. Experimental nests in more accessible locations and containing an odorous bait were more exposed to rodent predation. Apparently, the fan-tailed gerygone has either never been specifically vulnerable to predation by rats or has developed anti-predator adaptations.     

PEtab—Interoperable specification of parameter estimation problems in systems biology

Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been—so far—no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies.     

Cardamonin Presents in Vivo Activity against Schistosoma mansoni and Inhibits Potato Apyrase

Schistosomiasis, a neglected tropical disease caused by Schistosoma species, harms over 250 million people in several countries. The treatment is achieved with only one drug, praziquantel. Cardamonin, a natural chalcone with in vitro schistosomicidal activity, has not been in vivo evaluated against Schistosoma. In this work, we evaluated the in vivo schistosomicidal activities of cardamonin against Schistosoma mansoni worms and conducted enzymatic apyrase inhibition assay, as well as molecular docking analysis of cardamonin against potato apyrase, S. mansoni NTPDase 1 and S. mansoni NTPDase 2. In a mouse model of schistosomiasis, the oral treatment with cardamonin (400 mg/kg) showed efficacy against S. mansoni, decreasing the total worm load in 46.8 % and reducing in 54.5 % the number of eggs in mice. Cardamonin achieved a significant inhibition of the apyrase activity and the three-dimensional structure of the potato apyrase, obtained by homology modeling, showed that cardamonin may interact mainly through hydrogen bonds. Molecular docking studies corroborate with the action of cardamonin in binding and inhibiting both potato apyrase and S. mansoni NTPDases.     

Synthetic Aurones: New Features for Schistosoma mansoni Therapy

In this work, two synthetic aurones revealed moderate schistosomicidal potential in in vitro and in vivo assays. Aurones ( 1 ) and ( 2 ) promoted changes in tegument integrity and motor activity, leading to death of adult Schistosoma mansoni worms in in vitro assays. When administered orally (two doses of 50 mg/kg) in experimentally infected animals, synthetic aurones ( 1 ) and ( 2 ) promoted reductions of 56.20 % and 57.61 % of the parasite load and stimulated the displacement towards the liver of the remaining adult worms. The oogram analysis revealed that the treatment with both aurones interferes with the egg development kinetics in the intestinal tissue. Seeking an action target for compounds ( 1 ) and ( 2 ), the connection with NTPDases enzymes, recognized as important therapeutic targets for S. mansoni, was evaluated. Molecular docking studies have shown promising results. The dataset reveals the anthelmintic character of these compounds, which can be used in the development of new therapies for schistosomiasis.