Segregating the functions of human hippocampus

It is now accepted that hippocampal lesions impair episodic memory. However, the precise functional role of the hippocampus in episodic memory remains elusive. Recent functional imaging data implicate the hippocampus in processing novelty, a finding supported by human in vivo recordings and event-related potential studies. Here we measure hippocampal responses to novelty, using functional MRI (fMRI), during an item-learning paradigm generated from an artificial grammar system. During learning, two distinct types of novelty were periodically introduced: perceptual novelty, pertaining to the physical characteristics of stimuli (in this case visual characteristics), and exemplar novelty, reflecting semantic characteristics of stimuli (in this case grammatical status within a rule system). We demonstrate a left anterior hippocampal response to both types of novelty and adaptation of these responses with stimulus familiarity. By contrast to these novelty effects, we also show bilateral posterior hippocampal responses with increasing exemplar familiarity. These results suggest a functional dissociation within the hippocampus with respect to the relative familiarity of study items. Neural responses in anterior hippocampus index generic novelty, whereas posterior hippocampal responses index familiarity to stimuli that have behavioral relevance (i.e., only exemplar familiarity). These findings add to recent evidence for functional segregation within the human hippocampus during learning.

Cladistic association analysis of Y chromosome effects on alcohol dependence and related personality traits

Association between Y chromosome haplotype variation and alcohol dependence and related personality traits was investigated in a large sample of psychiatrically diagnosed Finnish males. Haplotypes were constructed for 359 individuals using alleles at eight loci (seven microsatellite loci and a nucleotide substitution in the DYZ3 alphoid satellite locus). A cladogram linking the 102 observed haplotype configurations was constructed by using parsimony with a single-step mutation model. Then, a series of contingency tables nested according to the cladogram hierarchy were used to test for association between Y haplotype and alcohol dependence. Finally, using only alcohol-dependent subjects, we tested for association between Y haplotype and personality variables postulated to define subtypes of alcoholism—antisocial personality disorder, novelty seeking, harm avoidance, and reward dependence. Significant association with alcohol dependence was observed at three Y haplotype clades, with significance levels of P = 0.002, P = 0.020, and P = 0.010. Within alcohol-dependent subjects, no relationship was revealed between Y haplotype and antisocial personality disorder, novelty seeking, harm avoidance, or reward dependence. These results demonstrate, by using a fully objective association design, that differences among Y chromosomes contribute to variation in vulnerability to alcohol dependence. However, they do not demonstrate an association between Y haplotype and the personality variables thought to underlie the subtypes of alcoholism.

A test of alternative models of diversification in tropical rainforests: Ecological gradients vs. rainforest refugia

Comparison of mitochondrial and morphological divergence in eight populations of a widespread leaf-litter skink is used to determine the relative importance of geographic isolation and natural selection in generating phenotypic diversity in the Wet Tropics Rainforest region of Australia. The populations occur in two geographically isolated regions, and within each region, in two different habitats (closed rainforest and tall open forest) that span a well characterized ecological gradient. Morphological differences among ancient geographic isolates (separated for several million years, judging by their mitochondrial DNA sequence divergence) were slight, but morphological and life history differences among habitats were large and occurred despite moderate to high levels of mitochondrial gene flow. A field experiment identified avian predation as one potential agent of natural selection. These results indicate that natural selection operating across ecological gradients can be more important than geographic isolation in similar habitats in generating phenotypic diversity. In addition, our results indicate that selection is sufficiently strong to overcome the homogenizing effects of gene flow, a necessary first step toward speciation in continuously distributed populations. Because ecological gradients may be a source of evolutionary novelty, and perhaps new species, their conservation warrants greater attention. This is particularly true in tropical regions, where most reserves do not include ecological gradients and transitional habitats.

Mutators and sex in bacteria: Conflict between adaptive strategies

Bacterial mutation rates can increase and produce genetic novelty, as shown by in vitro and in silico experiments. Despite the cost due to a heavy deleterious mutation load, mutator alleles, which increase the mutation rate, can spread in asexual populations during adaptation because they remain associated with the rare favorable mutations they generate. This indirect selection for a genetic system generating diversity (second-order selection) is expected to be highly sensitive to changes in the dynamics of adaptation. Here we show by a simulation approach that even rare genetic exchanges, such as bacterial conjugation or transformation, can dramatically reduce the selection of mutators. Moreover, drift or competition between the processes of mutation and recombination in the course of adaptation reveal how second-order selection is unable to optimize the rate of generation of novelty.

Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions

The evolution of novelty in tightly integrated biological systems, such as hormones and their receptors, seems to challenge the theory of natural selection: it has not been clear how a new function for any one part (such as a ligand) can be selected for unless the other members of the system (e.g., a receptor) are already present. Here I show—based on identification and phylogenetic analysis of steroid receptors in basal vertebrates and reconstruction of the sequences and functional attributes of ancestral proteins—that the first steroid receptor was an estrogen receptor, followed by a progesterone receptor. Genome mapping and phylogenetic analyses indicate that the full complement of mammalian steroid receptors evolved from these ancient receptors by two large-scale genome expansions, one before the advent of jawed vertebrates and one after. Specific regulation of physiological processes by androgens and corticoids are relatively recent innovations that emerged after these duplications. These findings support a model of ligand exploitation in which the terminal ligand in a biosynthetic pathway is the first for which a receptor evolves; selection for this hormone also selects for the synthesis of intermediates despite the absence of receptors, and duplicated receptors then evolve affinity for these substances. In this way, novel hormone-receptor pairs are created, and an integrated system of increasing complexity elaborated. This model suggests that ligands for some “orphan” receptors may be found among intermediates in the synthesis of ligands for phylogenetically related receptors.

Glucocorticoids have state-dependent stimulant effects on the mesencephalic dopaminergic transmission.

An increase in the activity of mesencephalic dopaminergic neurons has been implicated in the appearance of pathological behaviors such as psychosis and drug abuse. Several observations suggest that glucocorticoids might contribute to such an increase in dopaminergic activity. The present experiments therefore analyzed the effects of corticosterone, the major glucocorticoid in the rat, both on dopamine release in the nucleus accumbens of freely moving animals by means of microdialysis, and on locomotor activity, a behavior dependent on accumbens dopamine. Given that glucocorticoids have certain state-dependent neuronal effects, their action on dopamine was studied in situations differing in dopaminergic tonus, including during the light and dark phases of the circadian cycle, during eating, and in groups of animals differing in their locomotor reactivity to novelty. Dopaminergic activity is increased in the dark period, further increased during food-intake, and is higher in rats defined as high responders to novelty than in low responders. Corticosterone, peripherally administered in a dose that approximates stress-induced plasma concentrations, increased extracellular concentrations of dopamine, and this increase was augmented in the dark phase, during eating, and in high responder rats. Corticosterone had little or no effects in the light phase and in low responder rats. Corticosterone also stimulated locomotor activity, an effect that paralleled the release of dopamine and was abolished by neurochemical (6-hydroxydopamine) depletion of accumbens dopamine. In conclusion, glucocorticoids have state-dependent stimulant effects on mesencephalic dopaminergic transmission, and an interaction between these two factors might be involved in the appearance of behavioral disturbances.

Recruitment and replacement of hippocampal neurons in young and adult chickadees: an addition to the theory of hippocampal learning.

We used [3H]thymidine to document the birth of neurons and their recruitment into the hippocampal complex (HC) of juvenile (4.5 months old) and adult blackcapped chickadees (Parus atricapillus) living in their natural surroundings. Birds received a single dose of [3H]thymidine in August and were recaptured and killed 6 weeks later, in early October. All brains were stained with Cresyl violet, a Nissl stain. The boundaries of the HC were defined by reference to the ventricular wall, the brain surface, or differences in neuronal packing density. The HC of juveniles was as large as or larger than that of adults and packing density of HC neurons was 31% higher in juveniles than in adults. Almost all of the 3H-labeled HC neurons were found in a 350-m-wide layer of tissue adjacent to the lateral ventricle. Within this layer the fraction of 3H-labeled neurons was 50% higher in juveniles than in adults. We conclude that the HC of juvenile chickadees recruits more neurons and has more neurons than that of adults. We speculate that juveniles encounter greater environmental novelty than adults and that the greater number of HC neurons found in juveniles allows them to learn more than adults. At a more general level, we suggest that (i) long-term learning alters HC neurons irreversibly; (ii) sustained hippocampal learning requires the periodic replacement of HC neurons; (iii) memories coded by hippocampal neurons are transferred elsewhere before the neurons are replaced.

Genetic variation in vulnerability to the behavioral effects of neonatal hippocampal damage in rats.

We explored how two independent variables, one genetic (i.e., specific rat strains) and another environmental (i.e., a developmental excitotoxic hippocampal lesion), contribute to phenotypic variation. Sprague-Dawley (SD), Fischer 344 (F344), and Lewis rats underwent two grades of neonatal excitotoxic damage: small and large ventral hippocampal (SVH and LVH) lesions. Locomotion was tested before puberty [postnatal day 35 (P35)] and after puberty (P56) following exposure to a novel environment or administration of amphetamine. The behavioral effects were strain- and lesion-specific. As shown previously, SD rats with LVH lesions displayed enhanced spontaneous and amphetamine-induced locomotion as compared with controls at P56, but not at P35. SVH lesions in SD rats had no effect at any age. In F344 rats with LVH lesions, enhanced spontaneous and amphetamine-induced locomotion appeared early (P35) and was exaggerated at P56. SVH lesions in F344 rats resulted in a pattern of effects analogous to LVH lesions in SD rats--i.e., postpubertal onset of hyperlocomotion (P56). In Lewis rats, LVH lesions had no significant effect on novelty- or amphetamine-induced locomotion at any age. These data show that the degree of genetic predisposition and the extent of early induced hippocampal defect contribute to the particular pattern of behavioral outcome. These results may have implications for modeling interactions of genetic and environmental factors involved in schizophrenia, a disorder characterized by phenotypic heterogeneity, genetic predisposition, a developmental hippocampal abnormality, and vulnerability to environmental stress.

Espinosa: potência natural e seus reflexos no direito e na política

Este trabalho versa sobre o conceito de potência natural em Espinosa, sua amplitude e abrangência e seus reflexos no direito natural e na política. Procura revelar a originalidade do conceito de direito natural em Espinosa, muito diferente dos pontos de vista de Grotius, de Hobbes e de todos os demais filósofos e doutrinadores, levando-o, também, a uma visão diferente sobre a formação do Estado; e, finalmente, a sua doutrina sobre o Estado e suas diversas instituições políticas, enfatizando sempre a liberdade e a dignidade humanas como a razão de ser da criação desse mesmo Estado. Procuramos também revelar neste modesto trabalho o avanço, a novidade e a contribuição de Espinosa à ciência jurídica contemporânea.

GEOFIER: um sistema de anotação geográfica de textos com o uso de classificadores de aprendizagem de máquina.

A anotação geográfica de documentos consiste na adoção de metadados para a identificação de nomes de locais e a posição de suas ocorrências no texto. Esta informação é útil, por exemplo, para mecanismos de busca. A partir dos topônimos mencionados no texto é possível identificar o contexto espacial em que o assunto do texto está inserido, o que permite agrupar documentos que se refiram a um mesmo contexto, atribuindo ao documento um escopo geográfico. Esta Dissertação de Mestrado apresenta um novo método, batizado de Geofier, para determinação do escopo geográfico de documentos. A novidade apresentada pelo Geofier é a possibilidade da identificação do escopo geográfico de um documento por meio de classificadores de aprendizagem de máquina treinados sem o uso de um gazetteer e sem premissas quanto à língua dos textos analisados. A Wikipédia foi utilizada como fonte de um conjunto de documentos anotados geograficamente para o treinamento de uma hierarquia de Classificadores Naive Bayes e Support Vector Machines (SVMs). Uma comparação de desempenho entre o Geofier e uma reimplementação do sistema Web-a-Where foi realizada em relação à determinação do escopo geográfico dos textos da Wikipédia. A hierarquia do Geofier foi treinada e avaliada de duas formas: usando topônimos do mesmo gazetteer que o Web-a-Where e usando n-gramas extraídos dos documentos de treinamento. Como resultado, o Geofier manteve desempenho superior ao obtido pela reimplementação do Web-a-Where.

Rivalidad en el mercado español de depósitos bancarios: la teoría de los grupos estratégicos

El objetivo de este trabajo consiste en examinar la rivalidad intra y entre grupos estratégicos de una industria. La literatura sobre la materia sugiere que las evidencias empíricas detectadas pueden verse afectadas por problemas operativos relacionados con la medición de la rivalidad. Como novedad, la metodología aplicada propone la utilización de dos enfoques de medición de la rivalidad, uno indirecto mediante la estimación de la variación conjetural, y una evaluación directa a través de las noticias sobre acciones y reacciones estratégicas detectadas en las publicaciones. La aplicación empírica realizada en el mercado español de depósitos bancarios no permite asegurar nada acerca de la mayor o menor rivalidad intra que entre grupos; pero los grupos estratégicos permiten predecir la forma en que cada entidad compite con las demás.

Elección de la duración del viaje vacacional: una aproximación con modelos de recuento

La duración del viaje vacacional es una decisión del turista con unas implicaciones fundamentales para las organizaciones turísticas, pero que ha recibido una escasa atención por la literatura. Además, los escasos estudios se han centrado en los destinos costeros, cuando el turismo de interior se está erigiendo como una alternativa importante en algunos países. El presente trabajo analiza los factores determinantes de la elección temporal del viaje turístico, distinguiendo el tipo de destino elegido -costa e interior-, y proponiendo varias hipótesis acerca de la influencia de las características de los individuos relacionadas con el destino, de las restricciones personales y de las características sociodemográficas. La metodología aplicada estima, como novedad en este tipo de decisiones, un Modelo Binomial Negativo Truncado que evita los sesgos de estimación de los modelos de regresión y el supuesto restrictivo de igualdad media-varianza del Modelo de Poisson. La aplicación empírica realizada en España sobre una muestra de 1.600 individuos permite concluir, por un lado, que el Modelo Binomial Negativo es más adecuado que el de Poisson para realizar este tipo de análisis. Por otro lado, las dimensiones determinantes de la duración del viaje vacacional son, para ambos destinos, el alojamiento en hotel y apartamento propio, las restricciones temporales, la edad del turista y la forma de organizar el viaje; mientras que el tamaño de la ciudad de residencia y el atributo “precios baratos” es un aspecto diferencial de la costa; y el alojamiento en apartamentos alquilados lo es de los destinos de interior.

Impacto de la estrategia de diversificación en la expansión a mercados exteriores sobre los resultados

El propósito de este trabajo consiste en examinar los determinantes de los resultados empresariales, derivados de la estrategia de diversificación en la expansión a mercados exteriores, en términos de los factores del mercado, del producto y de la empresa. Como novedad, la metodología aplicada utiliza el estudio del suceso ("event-study") para estimar los excesos de rentabilidad de las acciones generados en la Bolsa por una muestra de 35 noticias de expansión a mercados exteriores correspondientes a 11 empresas españolas diversificadas; así como el análisis de regresión para examinar el impacto de los factores del mercado, del producto y de la empresa sobre dichos excesos de rentabilidad. La aplicación empírica realizada en nuestro país permite detectar que, en promedio, el impacto de dichas noticias sobre la rentabilidad de las acciones es positivo, siendo sus determinantes la especialización del producto y el grado de desarrollo del país de destino.

El Gratis (1842-1843): aproximación al estudio de un periódico innovador

El presente trabajo expone el análisis de El Gratis, diario de anuncios publicado en 1842-43, algunas de cuyas características (aplicación de la ley del doble mercado, distribución gratuita de parte de los ejemplares, edición de un diario-cartel…) representan una verdadera novedad para la época y para la historia del periodismo decimonónico en España.

El bienestar en España: una perspectiva de largo plazo, 1850-1991

Los historiadores económicos han estimado tradicionalmente el bienestar en términos de renta por persona. Durante la última década se han publicado, sin embargo, diversos trabajos que utilizan otros indicadores. Siguiendo esta línea de investigación, el artículo contrasta cuatro indicadores del bienestar en España (renta per capita, índice de Desarrollo Humano, Índice Físico de Calidad de Vida y estatura), dos de los cuales son inéditos (IDH e IFCV). Los resultados complican el objeto de estudio, pero sirven para proponer algunas hipótesis que deben ser ratificadas o desmentidas por futuras investigaciones.