Unpredictable Sound Stress Model Causes Migraine-Like Behaviors in Mice With Sexual Dimorphism.

Migraine represents one of the major causes of disability worldwide and is more prevalent in women; it is also related to anxiety symptoms. Stress, such as sound stress, is a frequently reported trigger in migraine patients, but the underlying mechanisms are not fully understood. However, it is known that patients with migraine have higher levels of plasma inflammatory cytokines and calcitonin gene-related peptide (CGRP). Stress mediated by unpredictable sound is already used as a model of painful sensitization, but migraine-like behaviors and sexual dimorphism have not yet been evaluated. This study characterized nociception and anxiety-related symptoms after the induction of sound stress in mice. C57BL/6 mice (20-30 g) were exposed to unpredictable sound stress for 3 days, nonconsecutive days. We observed enhanced plasma corticosterone levels on day 1 after stress induction. First, 7 days after the last stress session, mice developed hind paw and periorbital mechanical allodynia, grimacing pain behavior, anxiety-like symptoms, and reduced exploratory behavior. The nociceptive and behavioral alterations detected in this model were mostly shown in female stressed mice at day 7 post-stress. In addition, on day 7 post-stress nociception, these behaviors were consistently abolished by the CGRP receptor antagonist olcegepant (BIBN4096BS, 100 mg/kg by intraperitoneal route) in female and male stressed mice. We also demonstrated an increase in interleukine-6 (IL-6), tumor necrosis factor (TNF-α), and CGRP levels in stressed mice plasma, with female mice showing higher levels compared to male mice. This stress paradigm allows further preclinical investigation of mechanisms contributing to migraine-inducing pain.

Administração (a)política? O retrato e os fatores de seleção do dirigente público / ¿Administración (a)política? El retrato y los factores de selección del dirigente público / (A)Political administration? The public managers portrait and selection factors

Resumo Este artigo centra-se na problemática sobre como os atores políticos e administrativos se relacionam, concentrando-se na seleção de altos funcionários públicos como peças-chave no processo de implementação de políticas públicas. Em relação à metodologia adotada, foram realizadas uma revisão da literatura e uma análise documental, bem como a aplicação de um questionário on-line para altos funcionários que ocupavam cargos gerenciais entre 2004 e 2011 (n = 964). Em todas as análises, foram considerados estatisticamente significativos os resultados dos testes de hipóteses, com um valor de p igual ou inferior a .05 (p ≤ .05). A análise permitiu confirmar dois componentes/critérios principais que estão na fonte da seleção de altos funcionários públicos (políticos e profissionais) e, dentro de cada um, os respetivos fatores que os compõem. Pudemos reconhecer que o componente político tem seu peso, mas não foi possível confirmar completamente a hipótese de que, em Portugal, os fatores que influenciaram a seleção de altos funcionários públicos eram predominantemente políticos.

Resumen Este documento respalda la problemática acerca de cómo los actores políticos y administrativos se relacionan, enfocando particularmente la selección de altos funcionarios públicos como clave en el proceso de implementación de políticas públicas. Con respecto a la metodología utilizada, se realizaron una revisión de la literatura y un análisis documental, así como la aplicación de un cuestionario online a altos funcionarios que ocuparon cargos gerenciales entre 2004 y 2011 (n = 964). En todos los análisis se consideraron estadísticamente relevantes los resultados de dos pruebas de hipótesis con un valor de p igual o inferior a .05 (p ≤ .05). El análisis permitió confirmar dos componentes/criterios principales que están en la fuente de la selección de altos funcionarios públicos (políticos y profesionales) y, dentro de cada uno, los respectivos factores que los componen. Pudimos reconocer que el componente político tiene su peso, pero no fue posible confirmar completamente la hipótesis de que, en Portugal, los factores que influyeron en la selección de los altos funcionarios públicos fueron principalmente políticos.

Abstract This article addresses the issue of how political and administrative actors relate to each other, focusing on the selection of Senior Civil Servants as key actors to implement public policies. A literature review and documental analysis were carried out, and an on-line questionnaire was applied to Senior Civil Servants in managerial positions in Portugal between 2004 and 2011 (n = 964). The results show that, in all cases, the p-value was equal or less than .05 (p ≤ .05). The analysis allowed us to confirm two main criteria used for the selection of Senior Civil Servants (political and professional) and their respective factors. Despite indicating that the political criterion somehow plays a role in the selection of public officials in Portugal, the study could not confirm the hypothesis that political factors are predominant when hiring senior civil servants in the country.

Comparative characterization of Viperidae snake venoms from Perú reveals two compositional patterns of phospholipase A2 expression.

Snake species within the Bothrops complex (sensu lato) are of medical relevance in Latin America, but knowledge on their venom characteristics is limited, or even unavailable, for some taxa. Perú harbors 17 species of pit vipers, within the genera Bothrops, Bothriechis, Bothrocophias, Porthidium, Crotalus, and Lachesis. This study compared the venoms of twelve species, through chromatographic and electrophoretic profiles, as well as proteolytic and phospholipase A2 (PLA2) activities. Also, proteomic profiles were analyzed for nine of the venoms using a shotgun approach. Results unveiled conspicuous differences in the expression of venom PLA2s among species, six of them presenting scarce levels as judged by RP-HPLC profiles. Since most species within the bothropoid lineage possess venoms with high to intermediate abundances of this protein family, our findings suggest the existence of a phenotypic duality in the expression of venom PLA2s within the Bothrops (sensu lato) complex. Bothrops barnetti and Bothrocophias andianus venoms, very scarce in PLA2s, were shown to lack significant myotoxic activity, highlighting that the observed variability in PLA2 expression bears toxicological correlations with effects attributed to these proteins. Finally, an attempt to identify phylogenetic relationships of bothropoid species from Perú presenting low- or high-PLA2 venom phenotypes showed an interspersed pattern, thus precluding a simple phylogenetic interpretation of this venom compositional dichotomy.

Comparative venomics of Brazilian coral snakes: Micrurus frontalis, Micrurus spixii spixii, and Micrurus surinamensis.

A comparative venom proteomic analysis of the Brazilian southern coral snake, M. frontalis, the Amazon coral snake M. spixii spixii, and the aquatic coral snake M. surinamensis is reported. Venoms from M. frontalis and M. s. spixii were composed mainly (>90% of the total venom proteome) by 3FTxs and PLA2s in different proportions, and minor proteins from 2 to 5 protein families. Conversely, the aquatic coral snake expressed a streamlined (95%) 3FTx venom with low abundance (4.2%) of PLA2 molecules. A compositional-lethal activity for natural prey correlation analysis suggests that M. surinamensis venom may has evolved under strong pressure to quickly immobilize aquatic prey. On the other hand, venoms from M. frontalis and M. s. spixii, whose diet consist mainly of amphisbaenians and colubrid snakes, may have been shaped through balancing selection. Our work provides strong evidence for the occurrence in M. frontalis venom, but not in those from M. s. spixi and M. surinamensis, of a KUN-PLA2 complex homologue to heterodimeric venom toxins from some long-tailed monadal coral snakes that target acid-sensing receptors ASIC1a/2 evoking pain. The M. frontalis protein would represent the first example of a KUN-PLA2 heterodimer in a South American short-tailed triadal coral snake venom.

New insights into the phylogeographic distribution of the 3FTx/PLA2 venom dichotomy across genus Micrurus in South America.

Micrurus is a monophyletic genus of venomous coral snakes of the family Elapidae. The ~80 recognized species within this genus are endemic to the Americas, and are distributed from southeastern United States to northern Argentina. Although relatively few bites are recorded due to their reclusive nature, semi-fossorial habits, and their occurrence in sparsely populated areas, coral snakes possess powerful venoms that target the cholinergic system and, if early treatment is missed, can cause neuromuscular paralysis, respiratory failure, and death by asphyxiation within hours of envenoming. The to-date proteomically characterized 18 micrurine venoms exhibit a puzzling phenotypic dichotomy, characterized by the toxin arsenal being dominated either by pre-synaptically acting PLA2s or post-synaptic 3FTxs, and a general, but imperfect, distributional pattern of these venom phenotypes along the North-South axis of the American continent. The lack of perfect phylogenetic clustering suggests that phylogeny may not be the sole factor driving the evolution of the divergent venom phenotypes across Micrurus venoms. To shed new light on the origin and expression pattern of the 3FTx/PLA2 venom dichotomy, we have conducted a comparative proteomics analysis of venoms from the Brazilian ribbon coral snake, Micrurus lemniscatus carvalhoi, sourced from different localities in the Brazilian states of São Paulo; the Caatinga coral snake, M. ibiboboca, from central Bahia state (Brazil); two Micrurus specimens of uncertain taxonomy collected in the Brazilian states of Alagoas and Rio de Janeiro; and the Western ribbon coral snake, M. l. helleri, from Leticia, the southernmost town of the Colombian Department of Amazonas. Venoms from São Paulo and Rio de Janeiro showed 3FTx-predominant phenotypes, while in venoms from Leticia, Alagoas and Bahia PLA2s represented the major toxin family. Comparative venom proteomics suggests that both Micrurus venom phenotypes exhibit a high degree of toxin evolvability. Mapping the 3FTx/PLA2 dichotomy across the Americas points to a phylogeographic pattern for venom phenotypes consistent with, but more complex than, the North-South distribution hypothesis anticipated in previous investigations. BIOLOGICAL SIGNIFICANCE: New World coral snakes (Micrurus: Elapidae) produce potent venoms that target pre- and post-synaptically cholinergic nerve terminals resulting in neuromuscular paralysis, and in severe envenomings, may lead to death from asphyxiation by respiratory arrest. Presynaptic ß-neurotoxins of group IA PLA2 protein subfamily and postsynaptic α-neurotoxins with 3FTx fold are the major components (>80%) of coral snake venoms. Micrurine venoms exhibit a puzzling phenotypic venom dichotomy, characterized by the dominant expression of either α- or ß-neurotoxins. The distribution of these alternative compositional profiles has been fragmentarily studied both across Micrurus phylogeny and along the North-South axis of the genus radiation in the American continent, from southern United States to Northern Argentina. The unpredictability of the neurotoxin profile across the distribution range of the coral snakes represents a difficulty for applying the most appropriate treatment upon a coral snakebite. A deep knowledge of the phylogeographic distribution and the evolution of dichotomic Micrurus venoms would be useful for tracing the evolutionary path to their present day phenotypes, rationalizing the patchy cross-reactivity of current Micrurus antivenoms, and improving the efficacy of antivenoms to neutralize coral snake envenomings.

Infants' Characteristics and Skills: Dissolving the Nature/Nurture Dichotomy / Características e Competências dos Bebês: Rompendo a Dicotomia Inato/Aprendido / Características y Habilidades de los Bebés: Rompendo la Dicotomía Innato /Aprendido

Abstract According to an emergent group of researchers, systemic, relational and evolutionary thought is needed to understand the development of organisms' characteristics and competences. In this paper, we first introduce the prevalent view on the biological basis of behavior, based on the New Synthesis of Modern Biology. Next, we present the critical view of those who defend Extended Evolutionary Synthesis. The existing debate between the different perspectives is illustrated by studies on infants' sensorial capacities, attachment, and neonatal imitation. Possible interpretations, based on the theoretical approaches presented, lead to a reflection on the innate/acquired dichotomy: from the prevailing view, this dichotomy is overcome because the interaction between the innate and the acquired is being considered to explain the characteristics of living beings. A further reflection on the developmental processes involved in the emergence of behavior, on the concepts of what is learning and what is innate leads to the dissolution of this dichotomy.

Resumo Uma corrente emergente de pesquisadores vem defendendo que a compreensão sobre o desenvolvimento das características e competências dos organismos passa pela adoção de um pensamento sistêmico, relacional e também evolucionista. Com o objetivo de apresentar este pensamento, inicialmente discutimos a visão prevalente sobre as bases biológicas do comportamento, que se baseia na Nova Síntese da Biologia Moderna, e, a seguir, expomos a crítica colocada pelos defensores da Síntese Estendida da Evolução. Os debates entre as abordagens serão exemplificados por meio da apresentação de pesquisas sobre as capacidades sensoriais e estabelecimento de vínculo do bebê e a imitação neonatal. As interpretações possíveis, baseadas nas abordagens teóricas apresentadas, desembocam em uma reflexão sobre a dicotomia inato/adquirido: pela visão prevalente, esta dicotomia está superada porque a interação entre o inato e o adquirido vem sendo considerada para explicar as características dos seres vivos. Uma reflexão aprofundada sobre os processos de desenvolvimento envolvidos na emergência do comportamento ressignifica, no entanto, os conceitos de inato e aprendido, levando à dissolução desta dicotomia.

Resumen Una corriente emergente de investigadores viene defendiendo que la comprensión del desarrollo de los carácter y competencias de los organismos implica la adopción de un enfoque sistémico, relacional y evolucionista. Con el fin de presentar este argumento, en principio discutiremos la visión predominante sobre las bases biológicas del comportamiento, soportada en la Nueva Síntesis de la Biología Moderna y, a continuación, expondremos la crítica propuesta por los partidarios de la Síntesis Evolutiva Extendida. El debate entre los enfoques será ejemplificado a través de la presentación de investigaciones sobre capacidades sensoriales, el establecimiento del apego e imitación neonatal. Las posibles interpretaciones desde cada uno de los enfoques teóricos presentados desembocaran en una reflexión sobre la dicotomía innato/ adquirido: el punto de vista predominante sostiene que esta dicotomía se supera cuando se consideran las interacciones innato-adquirido. Una reflexión profunda sobre los procesos de desarrollo, involucrados en la emergencia del comportamiento, conduce a la disolución de la dicotomia innato-aprendido.

Assessing the geographic dichotomy hypothesis with cacti in South America.

The Cactaceae is one of the most conspicuous and ecologically important plant families in the world. Its species may have specialist or generalist pollination systems that show geographic patterns, which are synthesised in the Geographic Dichotomy Hypothesis. Here, we assess this hypothesis in five countries in both tropical and extratropical regions, evaluating the pollinator visitation rate and pollinator identity and abundance. We calculate the Shannon diversity index (H') and evenness (J) and evaluate differences between latitude parameters with a Student t-test. Overall, we found more specialised pollination systems in all tropical sites; the richness, diversity and evenness of pollinators was reduced in comparison to extratropical regions, where the pollination system was generalised. Our results support the geographic dichotomy hypothesis in the cacti of South America, suggesting that environmental factors underlying the latitudinal patterns can help to explain differences in the pollination syndrome between tropical and extratropical regions.

A dicotomia do Princípio da Integralidade do SUS / The SUS Completeness principle of dichotomy / La dicotomia del Principio de la Integralidad del SUS

Este artigo tem como objetivo discutir o aspecto dicotômico do princípio da integralidade, a partir de uma revisão literária narrativa. Apresenta um breve mapeamento histórico da luta pela saúde no mundo e no Brasil, como uma prática social. O princípio da integralidade como forma de ampliação ao acesso à saúde e, também, como forma de sua restrição. Finalizando com a análise das tentativas de arrefecimento desta dicotomia em contraste com a realidade social e econômica da sociedade brasileira.

This article aims to discuss the dichotomous aspect of the integrality principle, based on a literary narrative review. It presents a brief historical mapping of the struggle for health in the world and in Brazil, as a social practice. The principle of integrality as a way of expanding access to health and, also, as a form of its restriction. Finalizing with the analysis of attempts to cool this dichotomy in contrast to the social and economic reality of Brazilian society.

Este artículo tiene como objetivo discutir el aspecto dicotómico del principio de LA exhaustividad, a partir de una revisión narrativa literaria. Se presenta una historia de la lucha de la salud en el mundo y en Brasil, como una práctica social. El principio de la integralidad como medio para ampliar el acceso a la salud y también como una forma de restringir ellos. Al final con el análisis de esta dicotomía en contraste con la realidad social y económica de la sociedad brasileña.