QSARs of some novel isosteric heterocyclics with antifungal activity

QSAR analysis of a set of previously synthesized 2,5,6-trisubstituted benzoxazole, benzimidazole and 2-substituted oxazolo(4,5-b)pyridine derivatives tested for growth inhibitory activity against Candida albicans, was performed by using the computer-assisted multiple regression procedure. The activity contributions for either heterocyclic ring systems or substituent effects of these compounds were determined from the correlation equation and the predictions for the lead optimization were described. The resulting QSAR revealed that the oxazolo(4,5-b)pyridine ring system with the substitution of a benzyl moiety at position 2 was the most favourable structure among the heterocyclic nuclei. Moreover, the fifth position in the fused ring system is found more significant than the other positions in improving the activity.     

Pneumococcal vaccination and risk of myocardial infarction

Background

Based on promising results from laboratory studies, we hypothesized that pneumococcal vaccination would protect patients from myocardial infarction.

Methods

We conducted a hospital-based case–control study that included patients considered to be at risk of myocardial infarction. We used health databases to obtain hospital diagnoses and vaccination status. We compared patients who had been admitted for treatment of myocardial infarction with patients admitted to a surgical department in the same hospital for a reason other than myocardial infarction between 1997 and 2003.

Results

We found a total of 43 209 patients who were at risk; of these, we matched 999 cases and 3996 controls according to age, sex and year of hospital admission. Cases were less likely than controls to have been vaccinated (adjusted odds ratio [OR] 0.53, 95% confidence interval [CI] 0.40–0.70). This putative protective role of the vaccine was not observed for patients who had received the vaccine up to 1 year before myocardial infarction (adjusted OR 0.85, 95% CI 0.54–1.33). In contrast, if vaccination had occurred 2 years or more before the hospital admission, the association was stronger (adjusted OR 0.33, 95% CI 0.20–0.46).

Interpretation

Pneumococcal vaccination was associated with a decrease of more than 50% in the rate myocardial infarction 2 years after exposure. If confirmed, this association should generate interest in exploring the putative mechanisms and may offer another reason to promote pneumococcal vaccination.Despite important advances in primary prevention, atherosclerosis remains the leading cause of death in developed societies.¹ In addition to risk factors such as hypertension, diabetes mellitus, tobacco use and dyslipidemia, less traditional risk factors have also been sought. Many markers, including C-reactive protein and interleukins, highlight inflammation as a key mediator in both the progression and activation of atherosclerotic lesions.^2–4 Some medications that are used to prevent cardiovascular diseases, such as statins, also appear to reduce inflammation.⁵Animal experiments have shown that pneumococcal vaccination reduces the extent of atherosclerotic lesions.⁶ We hypothesized that antibodies directed against Streptococcus pneumoniae also recognize oxidized low-density lipoprotein (LDL) and impede the formation of foam cells. Interestingly, a retrospective cohort study involving World War II veterans who had undergone splenectomy documented excess mortality rates from both pneumonia and ischemic heart disease.⁷ More recent data have suggested that acute pneumococcal infections, but not vaccinations, increase the risk of vascular events;⁸ however, the duration of vaccination exposure considered in that study was limited.Our primary objective was to evaluate the association between pneumococcal vaccination and the risk of myocardial infarction. We also explored whether any effect of vaccination on the risk of infarction waned over time.     

Memory in the grip of emotions and stress: a necessarily harmful impact?

While intense negative events are vividly recalled, information learned during stressful situations is poorly remembered. These differential effects of emotions and stress on memory have been attributed to the physiological manifestations generated during those affective states. Intense emotional and stressful events trigger the secretion of catecholamines and of glucocorticoids, in particular. These hormones would be modulatory agents of memory functions. In the first part of this paper, we review the specific effects emotions and stress have on memory. We then summarize the psychological and biological determinants responsible for these effects. Finally, we discuss different methodological issues that could explain the discrepancy found between the impact of emotions and stress on memory. Defining more precisely the effects emotion and stress have on memory will lead to a better comprehension of the cognitive problems that characterize patients dealing with emotional turmoil, such as patients suffering from depression or post-traumatic stress disorder.     

Population dynamics of Aceodromus convolvuli (Acari: Mesostigmata: Blattisociidae) on spontaneous plants associated with Jatropha curcas in central Brazil

Spontaneously growing plants are commonly considered competitors of cultivated plants. Owing to the lack of specificity of many arthropods, spontaneous plants may be attacked by the same arthropods that attack cultivated plants and they may also harbor natural enemies of organisms harmful to cultivated plants. Aceodromus convolvuli Muma (Blattisociidae) has been reported recently in relatively large numbers in Tocantins state, central Brazil, mostly on Helicteres guazumifolia Kunth (Malvaceae). Very little has been reported about the population dynamics of blattisociid mites under field conditions. The objective of this work was to study the population dynamics of A. convolvuli in Gurupi, Tocantins state, to evaluate its possible interaction with associated mites. Monthly samples were taken from leaves of the 11 most abundant and frequent spontaneous plants in a Jatropha curcas L. (Euphorbiaceae) plantation. About 96.5 % of the specimens of A. convolvuli were collected in the rainy season. The patterns of variation of the population of A. convolvuli and of predators belonging to the family Phytoseiidae were similar, but A. convolvuli was much more numerous than all phytoseiid specimens combined. Highly significant correlations were observed between A. convolvuli densities and relative humidity or diversity of spontaneous plants. When only mites on H. guazumifolia were considered, highly significant correlation was also observed between densities of A. convolvuli and of mites of the family Tetranychidae. The results suggested that A. convolvuli could be a predator of tenuipalpid and/or tetranychid mites. Studies about its biology are needed to determine its preferred food sources and potential as biological control agent.     

Guarana (Paullinia cupana var. sorbilis), an anciently consumed stimulant from the Amazon rain forest: the seeded-fruit transcriptome

Guarana (Paullinia cupana var. sorbilis) is a plant native to the central Amazon basin. Roasted seed extracts have been used as medicinal beverages since pre-Colombian times, due to their reputation as stimulants, aphrodisiacs, tonics, as well as protectors of the gastrointestinal tract. Guarana plants are commercially cultivated exclusively in Brazil to supply the national carbonated soft-drink industry and natural product stores around the world. In this report, we describe and discuss the annotation of 15,387 ESTs from guarana seeded-fruits, highlighting sequences from the flavonoid and purine alkaloid pathways, and those related to biotic stress avoidance. This is the largest set of sequences registered for the Sapindaceae family.     

Induction medium osmolality improves microspore embryogenesis in wheat and triticale

The objective of this study was to determine the effect of induction medium osmolality on embryogenesis and green plant production in wheat and triticale. Isolated microspores of wheat and triticale were subjected to a range of osmolality (300–500 mOsm kg^?1) using mannitol. In both species, the maximum number of embryo-like structures (ELS) and green plants were obtained at 350 mOsm kg^?1 when the induction medium was supplemented with 9.1 g L^?1 of mannitol. A sharp decline in microspore response was observed at higher osmolality. These results demonstrate the effect of osmolality on induction of ELS and production of green plants indicating that the process of microspore embryogenesis can be improved in wheat and triticale by increasing osmolality of the induction medium to 350 mOsm kg^?1.     

The effect of cleaning and disinfecting the sampling well on the microbial communities of deep subsurface water samples

Our knowledge of the microbial characteristics of deep subsurface waters is currently very limited, mainly because of the methods used to collect representative microbial samples from such environments. In order to improve this procedure, a protocol designed to remove the unspecific, contaminant biofilm present on the walls of an approximately 800 m deep well is proposed. This procedure included extensive purges of the well, a mechanical cleaning of its wall, and three successive chlorine injections to disinfect the whole line before sampling. Total bacterial counts in water samples decreased from 2.5 x 10(5) to 1.0 x 10(4) per millilitre during the cleaning procedure. Culture experiments showed that the first samples were dominated by sulfate-reducers and heterotrophs, whereas the final sample was dominated by oligotrophic and hydrogenotrophic bacteria. Community structures established on the diversity of the 16S rRNA genes and data analysis revealed that the water sample collected, after a purge without removal of the biofilm, was characterized by numerous phyla which are not representative of the deep subsurface water. On the other hand, several bacterial phyla were only detected after the full cleaning of the well, and were considered as important components of the subsurface ecosystem which would have been missed in the absence of well cleaning.     

The Arabidopsis ATNRT2.7 nitrate transporter controls nitrate content in seeds

In higher plants, nitrate is taken up by root cells where Arabidopsis thaliana NITRATE TRANSPORTER2.1 (ATNRT2.1) chiefly acts as the high-affinity nitrate uptake system. Nitrate taken up by the roots can then be translocated from the root to the leaves and the seeds. In this work, the function of the ATNRT2.7 gene, one of the seven members of the NRT2 family in Arabidopsis, was investigated. High expression of the gene was detected in reproductive organs and peaked in dry seeds. beta-Glucuronidase or green fluorescent protein reporter gene expression driven by the ATNRT2.7 promoter confirmed this organ specificity. We assessed the capacity of ATNRT2.7 to transport nitrate in Xenopus laevis oocytes or when it is expressed ectopically in mutant plants deficient in nitrate transport. We measured the impact of an ATNRT2.7 mutation and found no difference from the wild type during vegetative development. By contrast, seed nitrate content was affected by overexpression of ATNRT2.7 or a mutation in the gene. Finally, we showed that this nitrate transporter protein was localized to the vacuolar membrane. Our results demonstrate that ATNRT2.7 plays a specific role in nitrate accumulation in the seed.     

The osmoregulatory and the amino acid-regulated responses of system A are mediated by different signal transduction pathways

The osmotic response of system A for neutral amino acid transport has been related to the adaptive response of this transport system to amino acid starvation. In a previous study (Ruiz-Montasell, B., M. Gómez-Angelats, F.J. Casado, A. Felipe, J.D. McGivan, and M. Pastor-Anglada. 1994. Proc. Natl. Acad. Sci. USA. 91:9569-9573), a model was proposed in which both responses were mediated by different mechanisms. The recent cloning of several isoforms of system A as well as the elucidation of a variety of signal transduction pathways involved in stress responses allow to test this model. SAT2 mRNA levels increased after amino acid deprivation but not after hyperosmotic shock. Inhibition of p38 activity or transfection with a dominant negative p38 did not alter the response to amino acid starvation but partially blocked the hypertonicity response. Inhibition of the ERK pathway resulted in full inhibition of the adaptive response of system A and no increase in SAT2 mRNA levels, without modifying the response to hyperosmolarity. Similar results were obtained after transfection with a dominant negative JNK1. The CDK2 inhibitor peptide-II decreased the osmotic response in a dose-dependent manner but did not have any effect on the adaptive response of system A. In summary, the previously proposed model of up-regulation of system A after hypertonic shock or after amino acid starvation by separate mechanisms is now confirmed and the two signal transduction pathways have been identified. The involvement of a CDK-cyclin complex in the osmotic response of system A links the activity of this transporter to the increase in cell volume previous to the entry in a new cell division cycle.