Striatal pre- and postsynaptic profile of adenosine A2A receptor antagonists

Striatal adenosine A2A receptors (A2ARs) are highly expressed in medium spiny neurons (MSNs) of the indirect efferent pathway, where they heteromerize with dopamine D2 receptors (D2Rs). A2ARs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A1 receptors (A1Rs). It has been hypothesized that postsynaptic A2AR antagonists should be useful in Parkinson's disease, while presynaptic A2AR antagonists could be beneficial in dyskinetic disorders, such as Huntington's disease, obsessive-compulsive disorders and drug addiction. The aim or this work was to determine whether selective A2AR antagonists may be subdivided according to a preferential pre- versus postsynaptic mechanism of action. The potency at blocking the motor output and striatal glutamate release induced by cortical electrical stimulation and the potency at inducing locomotor activation were used as in vivo measures of pre- and postsynaptic activities, respectively. SCH-442416 and KW-6002 showed a significant preferential pre- and postsynaptic profile, respectively, while the other tested compounds (MSX-2, SCH-420814, ZM-241385 and SCH-58261) showed no clear preference. Radioligand-binding experiments were performed in cells expressing A2AR-D2R and A1R-A2AR heteromers to determine possible differences in the affinity of these compounds for different A2AR heteromers. Heteromerization played a key role in the presynaptic profile of SCH-442416, since it bound with much less affinity to A2AR when co-expressed with D2R than with A1R. KW-6002 showed the best relative affinity for A2AR co-expressed with D2R than co-expressed with A1R, which can at least partially explain the postsynaptic profile of this compound. Also, the in vitro pharmacological profile of MSX-2, SCH-420814, ZM-241385 and SCH-58261 was is in accordance with their mixed pre- and postsynaptic profile. On the basis of their preferential pre- versus postsynaptic actions, SCH-442416 and KW-6002 may be used as lead compounds to obtain more effective antidyskinetic and antiparkinsonian compounds, respectively.

Emergence of assortative mixing between clusters of cultured neurons

The analysis of the activity of neuronal cultures is considered to be a good proxy of the functional connectivity of in vivo neuronal tissues. Thus, the functional complex network inferred from activity patterns is a promising way to unravel the interplay between structure and functionality of neuronal systems. Here, we monitor the spontaneous self-sustained dynamics in neuronal cultures formed by interconnected aggregates of neurons (clusters). Dynamics is characterized by the fast activation of groups of clusters in sequences termed bursts. The analysis of the time delays between clusters' activations within the bursts allows the reconstruction of the directed functional connectivity of the network. We propose a method to statistically infer this connectivity and analyze the resulting properties of the associated complex networks. Surprisingly enough, in contrast to what has been reported for many biological networks, the clustered neuronal cultures present assortative mixing connectivity values, meaning that there is a preference for clusters to link to other clusters that share similar functional connectivity, as well as a rich-club core, which shapes a"connectivity backbone" in the network. These results point out that the grouping of neurons and the assortative connectivity between clusters are intrinsic survival mechanisms of the culture.

The effect of learning on the evolution of new courtship behavior: a simulation model

The fact that individuals learn can change the relationship between genotype and phenotype in the population, and thus affect the evolutionary response to selection. Here we ask how male ability to learn from female response affects the evolution of a novel male behavioral courtship trait under pre-existing female preference (sensory drive). We assume a courtship trait which has both a genetic and a learned component, and a two-level female response to males. With individual-based simulations we show that, under this scenario, learning generally increases the strength of selection on the genetic component of the courtship trait, at least when the population genetic mean is still low. As a consequence, learning not only accelerates the evolution of the courtship trait, but also enables it when the trait is costly, which in the absence of learning results in an adaptive valley. Furthermore, learning can enable the evolution of the novel trait in the face of gene flow mediated by immigration of males that show superior attractiveness to females based on another, non-heritable trait. However, rather than increasing monotonically with the speed of learning, the effect of learning on evolution is maximized at intermediate learning rates. This model shows that, at least under some scenarios, the ability to learn can drive the evolution of mating behaviors through a process equivalent to Waddington's genetic assimilation.

The Influence of Chronic and Situational Social Status on Stereotype Susceptibility

We tested whether stereotypical situations would affect low-status group members' performance more strongly than high-status group members'. Experiment 1 and 2 tested this hypothesis using gender as a proxy of chronic social status and a gender-neutral task thathas been randomly presented to favor boys (men superiority condition), favor girls (women superiority condition), or show no gender preference (control condition). Both experiments found that women's (Experiment 1) and girls' performance (Experiment 2) suffered more from the evoked stereotypes than did men's and boys' ones. This result was replicated in Experiment 3, indicating that short men (low-status group) were more affected compared to tallmen (high-status group). Additionally, men were more affected compared to women when they perceived height as a threat. Hence, individuals are more or less vulnerable to identity threats as a function of the chronic social status at play; enjoying a high status provides protection and endorsing a low one weakens individual performance in stereotypical situations.

Health care workers' influenza vaccination: motivations and mandatory mask policy

BACKGROUND: Vaccination of health care workers (HCW) against seasonal influenza (SI) is recommended but vaccination rate rarely reach >30%. Vaccination coverage against 2009 pandemic influenza (PI) was 52% in our hospital, whilst a new policy requiring unvaccinated HCW to wear a mask during patient care duties was enforced. AIMS: To investigate the determinants of this higher vaccination acceptance for PI and to look for an association with the new mask-wearing policy. METHODS: A retrospective cohort study, involving HCW of three critical departments of a 1023-bed, tertiary-care university hospital in Switzerland. Self-reported 2009-10 SI and 2009 PI vaccination statuses, reasons and demographic data were collected through a literature-based questionnaire. Descriptive statistics, uni- and multivariate analyses were then performed. RESULTS: There were 472 respondents with a response rate of 54%. Self-reported vaccination acceptance was 64% for PI and 53% for SI. PI vaccination acceptance was associated with being vaccinated against SI (OR 9.5; 95% CI 5.5-16.4), being a physician (OR 7.7; 95% CI 3.1-19.1) and feeling uncomfortable wearing a mask (OR 1.7; 95% CI 1.0-2.8). Main motives for refusing vaccination were: preference for wearing a surgical mask (80% for PI, not applicable for SI) and concerns about vaccine safety (64%, 50%) and efficacy (44%, 35%). CONCLUSIONS: The new mask-wearing policy was a motivation for vaccination but also offered an alternative to non-compliant HCW. Concerns about vaccine safety and efficiency and self-interest of health care workers are still main determinants for influenza vaccination acceptance. Better incentives are needed to encourage vaccination amongst non-physician HCW.

Determinants of male fitness: disentangling intra- and inter-sexual selection.

Both intra- and inter-sexual selection may crucially determine a male's fitness. Their interplay, which has rarely been experimentally investigated, determines a male's optimal reproductive strategy and thus is of fundamental importance to the understanding of a male's behaviour. Here we investigated the relative importance of intra- and inter-sexual selection for male fitness in the common lizard. We investigated which male traits predict a male's access to reproduction allowing for both selective pressures and comparing it with a staged mating experiment excluding all types of intra-sexual selection. We found that qualitatively better males were more likely to reproduce and that sexual selection was two times stronger when allowing for both selective pressures, suggesting that inter- and intra-sexual selection determines male fitness and confirming the existence of multi-factorial sexual selection. Consequently, to optimize fitness, males should trade their investment between the traits, which are important for inter- and intra-sexual selection.

Defensive Metabolites from Antarctic Invertebrates: Does Energetic Content Interfere with Feeding Repellence?

Many bioactive products from benthic invertebrates mediating ecological interactions have proved to reduce predation, but their mechanisms of action, and their molecular identities, are usually unknown. It was suggested, yet scarcely investigated, that nutritional quality interferes with defensive metabolites. This means that antifeedants would be less effective when combined with energetically rich prey, and that higher amounts of defensive compounds would be needed for predator avoidance. We evaluated the effects of five types of repellents obtained from Antarctic invertebrates, in combination with diets of different energetic values. The compounds came from soft corals, ascidians and hexactinellid sponges; they included wax esters, alkaloids, a meroterpenoid, a steroid, and the recently described organic acid, glassponsine. Feeding repellency was tested through preference assays by preparing diets (alginate pearls) combining different energetic content and inorganic material. Experimental diets contained various concentrations of each repellent product, and were offered along with control compound-free pearls, to the Antarctic omnivore amphipod Cheirimedon femoratus. Meridianin alkaloids were the most active repellents, and wax esters were the least active when combined with foods of distinct energetic content. Our data show that levels of repellency vary for each compound, and that they perform differently when mixed with distinct assay foods. The natural products that interacted the most with energetic content were those occurring in nature at higher concentrations. The bioactivity of the remaining metabolites tested was found to depend on a threshold concentration, enough to elicit feeding repellence, independently from nutritional quality.

Self-deception as affective coping. An empirical perspective on philosophical issues.

In the philosophical literature, self-deception is mainly approached through the analysis of paradoxes. Yet, it is agreed that self-deception is motivated by protection from distress. In this paper, we argue, with the help of findings from cognitive neuroscience and psychology, that self-deception is a type of affective coping. First, we criticize the main solutions to the paradoxes of self-deception. We then present a new approach to self-deception. Self-deception, we argue, involves three appraisals of the distressing evidence: (a) appraisal of the strength of evidence as uncertain, (b) low coping potential and (c) negative anticipation along the lines of Damasio's somatic marker hypothesis. At the same time, desire impacts the treatment of flattering evidence via dopamine. Our main proposal is that self-deception involves emotional mechanisms provoking a preference for immediate reward despite possible long-term negative repercussions. In the last part, we use this emotional model to revisit the philosophical paradoxes.

Estereosseletividade em reações eletródicas

This review discusses the present state of the art of the stereochemistry of electrochemical reactions. The extent of asymmetric induction is progressing, but in general diastereoselectivities and enantioselectivities remain behind those from chemical synthesis. In recent years, new methodological developments have been successful. Effects that play important roles in homogeneous chemistry have been used with success. Lack of expressive enantiomeric excess (ee) could be related to the absence of tightly organized structures during the reaction of interest. The highest ee might be expected for redox reactions where conformational preference in transition state plays the important role or for the ones performed while adsorbed on the electrode, and where the chiral element is also at the surface, either adsorbed or chemically bound to the surface and interacting directly with the substrate. Electroenzymatic synthesis has a promising future.

Security and Privacy in a Ubiquitous Information Screen

We expose the ubiquitous interaction between an information screen and its’ viewers mobile devices, highlights the communication vulnerabilities, suggest mitigation strategies and finally implement these strategies to secure the communication. The screen infers information preferences’ of viewers within its vicinity transparently from their mobile devices over Bluetooth. Backend processing then retrieves up-to-date versions of preferred information from content providers. Retrieved content such as sporting news, weather forecasts, advertisements, stock markets and aviation schedules, are systematically displayed on the screen. To maximise users’ benefit, experience and acceptance, the service is provided with no user interaction at the screen and securely upholding preferences privacy and viewers anonymity. Compelled by the personal nature of mobile devices, their contents privacy, preferences confidentiality, and vulnerabilities imposed by screen, the service’s security is fortified. Fortification is predominantly through efficient cryptographic algorithms inspired by elliptic curves cryptosystems, access control and anonymity mechanisms. These mechanisms are demonstrated to attain set objectives within reasonable performance.

Trans-equatorial migration and mixing in the wintering areas of a pelagic seabird

Despite increasing interest in long-distance migration, the wintering areas, migration corridors, and population mix in winter quarters of most pelagic marine predators are unknown. Here, we present the first study tracking migration movements of shearwaters through the non-breeding period. We used geolocators (global location sensing [GLS] units based on ambient light levels) to track 22 Cory's shearwaters (Calonectris diomedea) breeding in three different areas. Most birds wintered in one or more of three relatively small areas, all clearly associated with major coastal upwelling systems of the tropical and south Atlantic. Trans-equatorial movements were dominated by prevailing trade winds and westerlies, while calm, oligotrophic areas were avoided. Breeding populations clearly differed in their preference amongst the three major wintering areas, but showed substantial mixing. This illustrates the exceptional value of GLS, not only for determining and describing the influence of oceanographic features on migration patterns, but also for assessing population mix in winter quarters. This knowledge is essential to understanding the impacts of population-level threats, such as longlining, offshore windfarms, and oil spills on multiple breeding sites, and will be critical in devising conservation policies that guarantee the sustainable exploitation of the oceans.

Aeromonas surface glucan attached throught the O-antigen ligase represents a new way to obtain UDP-Glucose

We previously reported that A. hydrophila GalU mutants were still able to produce UDP-glucose introduced as a glucose residue in their lipopolysaccharide core. In this study, we found the unique origin of this UDP-glucose from a branched α-glucan surface polysaccharide. This glucan, surface attached through the O-antigen ligase (WaaL), is common to the mesophilic Aeromonas strains tested. The Aeromonas glucan is produced by the action of the glycogen synthase (GlgA) and the UDP-Glc pyrophosphorylase (GlgC), the latter wrongly indicated as an ADP-Glc pyrophosphorylase in the Aeromonas genomes available. The Aeromonas glycogen synthase is able to react with UDP or ADP-glucose, which is not the case of E. coli glycogen synthase only reacting with ADP-glucose. The Aeromonas surface glucan has a role enhancing biofilm formation. Finally, for the first time to our knowledge, a clear preference on behalf of bacterial survival and pathogenesis is observed when choosing to produce one or other surface saccharide molecules to produce (lipopolysaccharide core or glucan).

Learning Preferences with Kernel-Based Methods

Learning of preference relations has recently received significant attention in machine learning community. It is closely related to the classification and regression analysis and can be reduced to these tasks. However, preference learning involves prediction of ordering of the data points rather than prediction of a single numerical value as in case of regression or a class label as in case of classification. Therefore, studying preference relations within a separate framework facilitates not only better theoretical understanding of the problem, but also motivates development of the efficient algorithms for the task. Preference learning has many applications in domains such as information retrieval, bioinformatics, natural language processing, etc. For example, algorithms that learn to rank are frequently used in search engines for ordering documents retrieved by the query. Preference learning methods have been also applied to collaborative filtering problems for predicting individual customer choices from the vast amount of user generated feedback. In this thesis we propose several algorithms for learning preference relations. These algorithms stem from well founded and robust class of regularized least-squares methods and have many attractive computational properties. In order to improve the performance of our methods, we introduce several non-linear kernel functions. Thus, contribution of this thesis is twofold: kernel functions for structured data that are used to take advantage of various non-vectorial data representations and the preference learning algorithms that are suitable for different tasks, namely efficient learning of preference relations, learning with large amount of training data, and semi-supervised preference learning. Proposed kernel-based algorithms and kernels are applied to the parse ranking task in natural language processing, document ranking in information retrieval, and remote homology detection in bioinformatics domain. Training of kernel-based ranking algorithms can be infeasible when the size of the training set is large. This problem is addressed by proposing a preference learning algorithm whose computation complexity scales linearly with the number of training data points. We also introduce sparse approximation of the algorithm that can be efficiently trained with large amount of data. For situations when small amount of labeled data but a large amount of unlabeled data is available, we propose a co-regularized preference learning algorithm. To conclude, the methods presented in this thesis address not only the problem of the efficient training of the algorithms but also fast regularization parameter selection, multiple output prediction, and cross-validation. Furthermore, proposed algorithms lead to notably better performance in many preference learning tasks considered.

Bromofenóis simples relacionados ao "flavor" de organismos marinhos

The perception of the flavor is an important attribute of quality in marine fish and other seafoods, being the first and main factor of discrimination for the evaluation, later acceptance and preference of the product by the consumer. Recently, the simple bromophenols have been considered an important group of key flavor compounds occurring in a wide variety of seafood species like fishes, mollusks, crustaceans and algae. When present in high concentration, in seafood, the bromophenols produce an undesirable flavor and are associated with inferior quality. Meanwhile, when present in low concentration levels (for example ng g-1) these compounds produce a desirable marine - or ocean-like - flavor and enhance the existing flavor in seafood. Indeed, simple bromophenols are widespread in seafood but virtually absent in freshwater fish. Herein we present a review on these flavor components found in the marine environment.

Empirical welfare analysis: when preferences matter

Fleurbaey and Maniquet have proposed the criteria of conditional equality and of egalitarian equivalence to assess the equity among individuals in an ordinal setting. Empirical applications are rare and only partially consistent with their framework. We propose a new empirical approach that relies on individual preferences, is consistent with the ordinal criteria and enables to compare them with the cardinal criteria. We estimate a utility function that incorporates individual heterogeneous preferences, obtain ordinal measures of well-being and apply conditional equality and egalitarian equivalence. We then propose two cardinal measures of well-being, that are comparable with the ordinal model, to compute Roemer’s and Van de gaer’s criteria. Finally we compare the characteristics of the worst-off displayed by each criterion. We apply this model to a sample of US micro data and obtain that about 18% of the worst-off are not common to all criteria.