Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence.

The azole antifungal fluconazole possesses only fungistatic activity in Candida albicans and, therefore, this human pathogen is tolerant to this agent. However, tolerance to fluconazole can be inhibited when C. albicans is exposed to fluconazole combined with the immunosuppressive drug cyclosporin A, which is known to inhibit calcineurin activity in yeast. A mutant lacking both alleles of a gene encoding the calcineurin A subunit (CNA) lost viability in the presence of fluconazole, thus making calcineurin essential for fluconazole tolerance. Consistent with this observation, tolerance to fluconazole was modulated by calcium ions or by the expression of a calcineurin A derivative autoactivated by the removal of its C-terminal inhibitory domain. Interestingly, CNA was also essential for tolerance to other antifungal agents (voriconazole, itraconazole, terbinafine, amorolfine) and to several other metabolic inhibitors (caffeine, brefeldin A, mycophenolic acid, fluphenazine) or cell wall-perturbing agents (SDS, calcofluor white, Congo red), thus indicating that the calcineurin pathway plays an important role in the survival of C. albicans in the presence of external growth inhibitors. Several genes, including PMC1, a vacuolar calcium P-type ATPase, were regulated in a calcineurin- and fluconazole-dependent manner. However, PMC1 did not play a direct role in the survival of C. albicans when exposed to fluconazole. In addition to these different properties, calcineurin was found to affect colony morphology in several media known to modulate the C. albicans dimorphic switch. In particular, calcineurin was found to be essential for C. albicans viability in serum-containing media. Finally, calcineurin was found to be necessary for the virulence of C. albicans in a mice model of infection, thus making calcineurin an important element for adequate adaptation to the conditions of the host environment.

Nanotechnology: balancing benefits and risks to public health and the environment : expert paper

Nanotechnology has been heralded as a "revolution" in science, for two reasons: first, because of its revolutionary view of the way in which chemicals and elements, such as gold and silver, behave, compared to traditional scientific understanding of their properties. Second, the impact of these new discoveries, as applied to commerce, can transform the daily life of consumer products ranging from sun tan lotions and cosmetics, food packaging and paints and coatings for cars, housing and fabrics, medicine and thousands of industrial processes.9 Beneficial consumer use of nanotechnologies, already in the stream of commerce, improves coatings on inks and paints in everything from food packaging to cars. Additionally, "Nanomedicine" offers the promise of diagnosis and treatment at the molecular level in order to detect and treat presymptomatic disease,10 or to rebuild neurons in Alzheimer's and Parkinson's disease. There is a possibility that severe complications such as stroke or heart attack may be avoided by means of prophylactic treatment of people at risk, and bone regeneration may keep many people active who never expected rehabilitation. Miniaturisation of diagnostic equipment can also reduce the amount of sampling materials required for testing and medical surveillance. Miraculous developments, that sound like science fiction to those people who eagerly anticipate these medical products, combined with the emerging commercial impact of nanotechnology applications to consumer products will reshape civil society - permanently. Thus, everyone within the jurisdiction of the Council of Europe is an end-user of nanotechnology, even without realising that nanotechnology has touched daily life.

The cave (La caverna -1952-1969) by Josep Palau i Fabre: theatre versus philosophical allegory in order both to perform and stop the tragic and dark end of the bright art of thinking

What is the use of representing in performance the image of the cave from book VII of Plato’s Republic? Josep Palau i Fabre considers that in Plato’s dialogues the speakers are mere instruments at the service of his dialectical purpose. The aim of this article is to show how, by turning the myth into a tragedy and relying on Heraclitus’s conflict or war of opposites, the playwright succeeds in favouring a sort of thought which is not one-sided or univocal. On the contrary, in Palau i Fabre’s La Caverna, the tragic hero, the released prisoner transformed by the light of Reality and finally killed by his “cavemates” –after having been imprisoned again and having tried to rescue them from their ignorance or shadows– still leaves them his powerful experience of the agonistikós thought, which might bear fruit in their life to come.

Myocardial tolerance to ischemia-reperfusion injury, training intensity and cessation.

Training has been shown to induce cardioprotection. The mechanisms involved remain still poorly understood. Aims of the study were to examine the relevance of training intensity on myocardial protection against ischemia/reperfusion (I/R) injury, and to which extent the beneficial effects persist after training cessation in rats. Sprague-Dawley rats trained at either low (60% [Formula: see text]) or high (80% [Formula: see text]) intensity for 10 weeks. An additional group of highly trained rats was detrained for 4 weeks. Untrained rats served as controls. At the end of treatment, rats of all groups were split into two subgroups. In the former, rats underwent left anterior descending artery (LAD) ligature for 30 min, followed by 90-min reperfusion, with subsequent measurement of the infarct size. In the latter, biopsies were taken to measure heat-shock proteins (HSP) 70/72, vascular endothelial growth factor (VEGF) protein levels, and superoxide dismutase (SOD) activity. Training reduced infarct size proportionally to training intensity. With detraining, infarct size increased compared to highly trained rats, maintaining some cardioprotection with respect to controls. Cardioprotection was proportional to training intensity and related to HSP70/72 upregulation and Mn-SOD activity. The relationship with Mn-SOD was lost with detraining. VEGF protein expression was not affected by either training or detraining. Stress proteins and antioxidant defenses might be involved in the beneficial effects of long-term training as a function of training intensity, while HSP70 may be one of the factors accounting for the partial persistence of myocardial protection against I/R injury in detrained rats.

Tolerance to preharvest sprouting and yield of wheat genotypes from different breeding programs

Abstract:The objective of this work was to characterize the performance of elite wheat genotypes from different Brazilian breeding programs for traits associated with grain yield and preharvest sprouting. The study was conducted in 2010 and 2011 in the municipality of Capão do Leão, in the state of Rio Grande do Sul, Brazil, in a randomized complete block design with three replicates. Thirty-three wheat genotypes were evaluated for traits related to preharvest sprouting and grain yield. The estimate of genetic distance was used to predict potential combinations for selection of plants with high grain yield and tolerance to preharvest sprouting. The combined analysis of sprouted grains and falling number shows that the TBIO Alvorada, TBIO Mestre, Frontana, Fundacep Raízes, Fundacep Cristalino, and BRS Guamirim genotypes are tolerant to preharvest sprouting. Combinations of TBIO Alvorada and TBIO Mestre with Fundacep Cristalino show high potential for recovering superior genotypes for high grain yield and tolerance to preharvest sprouting.

Tree cover at fine and coarse spatial grains interacts with shade tolerance to shape plant species distributions across the Alps

The role of competition for light among plants has long been recognized at local scales, but its potential importance for plant species' distribution at larger spatial scales has largely been ignored. Tree cover acts as a modulator of local abiotic conditions, notably by reducing light availability below the canopy and thus the performance of species that are not adapted to low-light conditions. However, this local effect may propagate to coarser spatial grains. Using 6,935 vegetation plots located across the European Alps, we fit Generalized Linear Models (GLM) for the distribution of 960 herbs and shrubs species to assess the effect of tree cover at both plot and landscape grain sizes (~ 10-m and 1-km, respectively). We ran four models with different combinations of variables (climate, soil and tree cover) for each species at both spatial grains. We used partial regressions to evaluate the independent effects of plot- and landscape-scale tree cover on plant communities. Finally, the effects on species' elevational range limits were assessed by simulating a removal experiment comparing the species' distribution under high and low tree cover. Accounting for tree cover improved model performance, with shade-tolerant species increasing their probability of presence at high tree cover whereas shade-intolerant species showed the opposite pattern. The tree cover effect occurred consistently at both plot and landscape spatial grains, albeit strongest at the former. Importantly, tree cover at the two grain sizes had partially independent effects on plot-scale plant communities, suggesting that the effects may be transmitted to coarser grains through meta-community dynamics. At high tree cover, shade-intolerant species exhibited elevational range contractions, especially at their upper limit, whereas shade-tolerant species showed elevational range expansions at both limits. Our findings suggest that the range shifts for herb and shrub species may be modulated by tree cover dynamics.

Mourning Becomes Electra by Eugene O’Neill: Aeschylus and Plato’s Cave to Create a Dark Drama

The fundamental debt of E. O’Neill’s Mourning Becomes Electra to Aeschylus, and to a lesser degree to Sophocles and Euripides, has been always recognised but, according to the author’s hypothesis, O’Neill might have taken advantage of the Platonic image of the cave in order to magnify his both Greek and American drama. It is certainly a risky hypothesis that stricto sensu cannot be proved, but it is also reader’s right to evaluate the plausibility and the possible dramatic benefit derived from such a reading. Besides indicating to what degree some of the essential themes of Platonic philosophy concerning darkness, light or the flight from the prison of the material world are not extraneous to O’Neill’s work, the author proves he was aware of the Platonic image of the cave thanks to its capital importance in the work of some of his intellectual mentors such as F. Nietzsche or Oscar Wilde. Nevertheless, the most significant aim of the author’s article is to emphasize both the dramatic benefits and the logical reflections derived, as said before, from reading little by little O’Neill’s drama bearing in mind the above mentioned Platonic parameter.

The Andean Biotic Index (ABI): revised tolerance to pollution values for macroinvertebrate families and index performance evaluation.

Score-based biotic indices are widely used to evaluate the water quality of streams and rivers. Few adaptations of these indices have been done for South America because there is a lack of knowledge on mac-roinvertebrate taxonomy, distribution and tolerance to pollution in the region. Several areas in the Andes are densely populated and there is need for methods to assess the impact of increasing human pressures on aquatic ecosystems. Considering the unique ecological and geographical features of the Andes, macroinvertebrate indices used in other regions must be adapted with caution. Here we present a review of the literature on mac-roinvertebrate distribution and tolerance to pollution in Andean areas above 2 000masl. Using these data, we propose an Andean Biotic Index (ABI), which is based on the BMWP index. In general, ABI includes fewer macroinvertebrate families than in other regions of the world where the BMWP index has been applied because altitude restricts the distribution of several families. Our review shows that in the high Andes, the tolerance of several macroinvertebrate families to pollution differs from those reported in other areas. We tested the ABI index in two basins in Ecuador and Peru, and compared it to other BMWP adaptations using the reference condi-tion approach. The ABI index is extremely useful for detecting the general impairment of rivers but class quality boundaries should be defined independently for each basin because reference conditions may be different. The ABI is widely used in Ecuador and Peru, with high correlations with land-use pressures in several studies. The ABI index is an integral part of the new multimetric index designed for high Andean streams (IMEERA). Rev. Biol. Trop. 62 (Suppl. 2): 249-273. Epub 2014 April 01.

Identification and application of bile metabolites to assess the exposure of fish to pharmaceuticals in the environment

Thousands of tons of pharmaceuticals are consumed yearly worldwide. Due to the continuous and increasing consumption and their incomplete elimination in wastewater treatment plants (WWTP), pharmaceuticals and their metabolites can be detected in receiving waters, although at low concentrations (ng to low μg/L). As bioactive molecules the presence of pharmaceuticals in the aquatic environment must be considered potentially hazardous for the aquatic organisms. In this thesis, the biotransformation and excretion of pharmaceuticals in fish was studied. The main biotransformation pathways of three anti‐inflammatory drugs, diclofenac, naproxen and ibuprofen, in rainbow trout were glucuronidation and taurine conjugation of the parent compounds and their phase I metabolites. The same metabolites were present in fish bile in aquatic exposures as in fish dosed with intraperitoneal injection. Higher bioconcentration factor in bile (BCFbile) was found for ibuprofen when compared to diclofenac and naproxen. Laboratory exposure studies were followed by a study of uptake of pharmaceuticals in a wild fish population living in lake contaminated with WWTP effluents. Of the analyzed 17 pharmaceuticals and six phase I metabolites, only diclofenac, naproxen and ibuprofen was present in bream and roach bile. It was shown, that diclofenac, naproxen and ibuprofen excreted by the liver can be found in rainbow trout and in two native fish species living in the receiving waters. In the bream and roach bile, the concentrations of diclofenac, naproxen and ibuprofen were roughly 1000 times higher than those found in the lake water, while in the laboratory exposures, the bioconcentration of the compounds and their metabolites in rainbow trout bile were at the same level as in wild fish or an order of magnitude higher. Thus, the parent compounds and their metabolites in fish bile can be used as a reliable biomarker to monitor the exposure of fish to environmental pharmaceuticals present in water receiving discharges from WWTPs.

A Study of African American Vernacular English in Three Novels and Colloquial Finnish in their Translations – The Dark Tower II: The Drawing of the Three, A Time to Kill and Push

Pro gradu -tutkielma käsittelee afroamerikkalaisen puhekielen (African American Vernacular English, AAVE) käyttöä kolmen englanninkielisen romaanin dialogissa ja suomen yleispuhekielen käyttöä romaanien käännöksissä. Tutkimus on pääasiassa kvantitatiivinen ja deskriptiivinen. Romaanit ovat Stephen Kingin The Dark Tower II: The Drawing of the Three (1987) (Musta torni 2, Kolme korttia pakasta 2005, suom. Kari Salminen), John Grishamin A Time to Kill (1989) (On aika tappaa 1994, suom. Kimmo Linkama) ja Sapphiren Push (1996) (Precious – harlemilaistytön tarina 2010, suom. Kristiina Drews). Alkukielisten romaanien osalta Grisham ja Sapphire suosivat lauseopillisia kielenpiirteitä, kun taas King on suosinut äänteellisiä. Sen sijaan käännöksissä piirteistä yleisimpiä ovat äänteelliset ja harvinaisimpia lauseopilliset. Vaikka käännöksissä sanastolliset piirteet ovat taajaan esiintyviä, äänteellisiä piirteitä esiintyy niitä enemmän. Poikkeuksena on On aika tappaa, jossa sanastollisia piirteitä esiintyy enemmän kuin äänteellisiä. Tulos eroaa Sampo Nevalaisen vuonna 2003 tekemästä tutkimuksesta, jossa hän sai selville, että käännöksissä käytetyt piirteet olivat enimmäkseen sanastollisia, kun taas alun perin suomeksi kirjoitetussa kaunokirjallisuudessa puhekielisyyden vaikutelma saatiin aikaan pääasiassa äänteellisin keinoin. Mahdollinen selitys tässä tutkimuksessa havaitulle erolle on se, että kahdessa romaanissa esiintyvä leimallinen AAVEn käyttö on saanut kääntäjät käyttämään samanlaisia strategioita kuin suomalaiset kirjailijat murretta kirjoittaessaan.

Effects of naltrexone and cross-tolerance to morphine in a learned helplessness paradigm

Opiates have been implicated in learned helplessness (LH), a phenomenon known to be related to opiate stress-induced analgesia (SIA). In the present study, we investigated the role of opiates in the induction of LH and SIA under different conditions. Adult female Wistar rats were trained either by receiving 60 inescapable 1-mA footshocks (IS group, N = 114) or by confinement in the shock box (control or NS group, N = 92). The pain threshold of some of the animals was immediately evaluated in a tail-flick test while the rest were used 24 h later in a shuttle box experiment to examine their escape performance. The opiate antagonist naltrexone (0 or 8 mg/kg, ip) and the previous induction of cross-tolerance to morphine by the chronic administration of morphine (0 or 10 mg/kg, sc, for 13 days) were used to identify opiate involvement. Analysis of variance revealed that only animals in the IS group demonstrated antinociception and an escape deficit, both of which were resistant to the procedures applied before the training session. However, the escape deficit could be reversed if the treatments were given before the test session. We conclude that, under our conditions, induction of the LH deficit in escape performance is not opiate-mediated although its expression is opiate-modulated

Natural preference of zebrafish (Danio rerio) for a dark environment

The zebrafish (Danio rerio) has been used as a model in neuroscience but knowledge about its behavior is limited. The aim of this study was to determine the preference of this fish species for a dark or light environment. Initially we used a place preference test and in a second experiment we applied an exit latency test. A two-chamber aquarium was used for the preference test. The aquarium consisted of a black chamber and a white chamber. In the first experiment the animal was placed in the aquarium and the time spent in the two compartments was recorded for 10 min. More time was spent in the black compartment (Wilcoxon matched-pairs signed-rank test, T = 7, N1 = N2 = 18, P = 0.0001). In the second experiment the animal was placed in the black or white compartment and the time it took to go from the initial compartment to the opposite one was recorded. The test lasted a maximum of 10 min. The results showed that the animal spent more time to go from the black to the white compartment (Mann-Whitney rank sum test, T = 48, N1 = 9, N2 = 8, P<0.0230). These data suggest that this fish species has a natural preference for a dark environment and this characteristic can be very useful for the development of new behavioral paradigms for fish.

Adaption of Courses and Learning Environment to the User Context in dotLRN

The explosive growth of Internet during the last years has been reflected in the ever-increasing amount of the diversity and heterogeneity of user preferences, types and features of devices and access networks. Usually the heterogeneity in the context of the users which request Web contents is not taken into account by the servers that deliver them implying that these contents will not always suit their needs. In the particular case of e-learning platforms this issue is especially critical due to the fact that it puts at stake the knowledge acquired by their users. In the following paper we present a system that aims to provide the dotLRN e-learning platform with the capability to adapt to its users context. By integrating dotLRN with a multi-agent hypermedia system, online courses being undertaken by students as well as their learning environment are adapted in real time