Behavioral decision making and the levels of change: An application of the transtheoretical model to prenatal smoking in low -income women

Despite continued research and public health efforts to reduce smoking during pregnancy, prenatal cessation rates in the United States have decreased and the incidence of low birth weight has increased from 1985 to 1991. Lower socioeconomic status women who are at increased risk for poor pregnancy outcomes may be resistant to current intervention efforts during pregnancy. The purpose of this dissertation was to investigate the determinants of continued smoking and quitting among low-income pregnant women.^ Using data from cross-sectional surveys of 323 low-income pregnant smokers, the first study developed and tested measures of the pros and cons of smoking during pregnancy. The original decisional balance measure for smoking was compared with a new measure that added items thought to be more salient to the target population. Confirmatory factor analysis using structural equation modeling showed neither the original nor new measure fit the data adequately. Using behavioral science theory, content from interviews with the population, and statistical evidence, two 7-item scales representing the pros and cons were developed from a portion (n = 215) of the sample and successfully cross-validated on the remainder of the sample (n = 108). Logistic regression found only pros were significantly associated with continued smoking. In a discriminant function analysis, stage of change was significantly associated with pros and cons of smoking.^ The second study examined the structural relationships between psychosocial constructs representing some of the levels of and the pros and cons of smoking. The cross-sectional design mandates that statements made regarding prediction do not prove causation or directionality from the data or methods analysis. Structural equation modeling found the following: more stressors and family criticism were significantly more predictive of negative affect than social support; a bi-directional relationship was found between negative affect and current nicotine addiction; and negative affect, addiction, stressors, and family criticism were significant predictors of pros of smoking.^ The findings imply reversing the trend of decreasing smoking cessation during pregnancy may require supplementing current interventions for this population of pregnant smokers with programs addressing nicotine addiction, negative affect, and other psychosocial factors such as family functioning and stressors. ^

Behavioral characteristics of applied general equilibrium models with an Armington-Krugman-Melitz encompassing module

This paper explore how simulation results change with different choice of trade specification, and the strength of preference for traded variety by economic agent differs, utilizing two types of three-region, three-sector AGE model that includes the Armington-Krugman-Melitz Encompassing module based on Dixon and Rimmer (2012). Simulation experiments reveal that: (1) the Melitz-type specification does not always enhance effectiveness of a certain policy change more than the one obtained with the Krugman-type, especially when economic agents' preference for traded variety is not so strong; (2) there are likely to be points where the volumes of effects obtained with the Melitz-type exceed the ones with the Krugman-type; and (3) the preference of the producers, those who are in the sectors that exhibit increasing returns to scale, for traded variety might be the engine of explosive effects as suggested by Fujita, et al. (2000).

Value, quality, purchasing habits and repurchase intention in B2C: differences between frequent and occasional purchasers

Este estudio propone un modelo integrador de la recompra en comercio electrónico (B2C), basado en la teoría de la confirmación de expectativas, tomando como partida el modelo de Bhattacherjee extendido con el modelo de satisfacción Cronin. El modelo de investigación se ha probado con 536 compradores españoles, usando análisis multigrupo. El modelo fue capaz de explicar más del setenta por ciento de la varianza de la intención de recompra. Como resultados, la relación entre la calidad y la satisfacción es no significativa para todos los tipos de consumidores y la relación entre la utilidad y la recompra es no significativa sólo para los compradores más frecuentes. Algunas ideas para llevar a la práctica son presentadas a modo de discusión.

Hybrid behavioral-analytical loss model for a high frequency and low load DC/DC buck converter

This work presents a behavioral-analytical hybrid loss model for a buck converter. The model has been designed for a wide operating frequency range up to 4MHz and a low power range (below 20W). It is focused on the switching losses obtained in the power MOSFETs. Main advantages of the model are the fast calculation time (below 8.5 seconds) and a good accuracy, which makes this model suitable for the optimization process of the losses in the design of a converter. It has been validated by simulation and experimentally with one GaN power transistor and three Si MOSFETs. Results show good agreement between measurements and the model

Importancia de los modelos de conducta en la intención emprendedora en estudiantes de ingeniería = The importance of role models for the entrepreneurial intention of technical degrees students

El emprendimiento de base tecnológica es un tema crítico para la generación de crecimiento económico, por lo que conocer los determinantes de la intención emprendedora de estudiantes de universidades técnicas adquiere una especial relevancia. En este estudio se analiza la importancia de los modelos de conducta en la intención emprendedora entre los estudiantes de carreras técnicas. Los resultados muestran que los estudiantes de padres empresarios tienen una intención emprendedora superior a la media, mientras que los de hijos de padres funcionarios están por debajo de ella. Igualmente, la ausencia de modelos de conducta emprendedora en el entorno cercano disminuye la intención emprendedora, mientras que la ausencia de funcionarios no la hace aumentar.

Comportamiento del paciente de la clínica dental. Modelo basado en la percepción de la calidad del servicio y fidelización del paciente

Esta tesis doctoral propone un modelo de comportamiento del paciente de la clínica dental, basado en la percepción de la calidad del servicio (SERVQUAL), la fidelización del paciente, acciones de Marketing Relacional y aspectos socioeconómicos relevantes, de los pacientes de clínicas dentales. En particular, el estudio de campo se lleva a cabo en el ámbito geográfico de la Comunidad de Madrid, España, durante los años 2012 y 2013. La primera parte del proceso de elaboración del modelo está basada en la recolección de datos. Para ello, se realizaron cinco entrevistas a expertos dentistas y se aplicaron dos tipos encuestas diferentes: una para el universo formado por el conjunto de los pacientes de las clínicas dentales y la otra para el universo formado el conjunto de los dentistas de las clínicas dentales de la Comunidad de Madrid. Se obtuvo muestras de: 200 encuestas de pacientes y 220 encuestas de dentistas activos colegiados en el Ilustre Colegio Oficial de Odontólogos y Estomatólogos de la I Región Madrid. En la segunda parte de la elaboración del modelo, se realizó el análisis de los datos, la inducción y síntesis del modelo propuesto. Se utilizó la metodología de modelos gráficos probabilísticos, específicamente, una Red Bayesiana, donde se integraron variables (nodos) y sus dependencias estadísticas causales (arcos dirigidos), que representan el conocimiento obtenido de los datos recopilados en las encuestas y el conocimiento derivado de investigaciones precedentes en el área. Se obtuvo una Red Bayesiana compuesta por 6 nodos principales, de los cuales dos de ellos son nodos de observación directa: “Revisit Intention” y “SERVQUAL”, y los otros cuatro nodos restantes son submodelos (agrupaciones de variables), estos son respectivamente: “Attitudinal”, “Disease Information”, “Socioeconomical” y “Services”. Entre las conclusiones principales derivadas del uso del modelo, como herramientas de inferencia y los análisis de las entrevistas realizadas se obtiene que: (i) las variables del nodo “Attitudinal” (submodelo), son las más sensibles y significativas. Al realizarse imputaciones particulares en las variables que conforman el nodo “Attitudinal” (“RelationalMk”, “Satisfaction”, “Recommendation” y “Friendship”) se obtienen altas probabilidades a posteriori en la fidelidad del paciente de la clínica dental, medida por su intención de revisita. (ii) En el nodo “Disease Information” (submodelo) se destaca la relación de dependencia causal cuando se imputa la variable “Perception of disease” en “SERVQUAL”, demostrando que la percepción de la gravedad del paciente condiciona significativamente la percepción de la calidad del servicio del paciente. Como ejemplo destacado, si se realiza una imputación en la variable “Clinic_Type” se obtienen altas probabilidades a posteriori de las variables “SERVQUAL” y “Revisit Intention”, lo que evidencia, que el tipo de clínica dental influye significativamente en la percepción de la calidad del servicio y en la fidelidad del paciente (intención de revisita). (iii) En el nodo “Socioeconomical” (submodelo) la variable “Sex” resultó no ser significativa cuando se le imputaban diferentes valores, por el contrario, la variable “Age” e “Income” mostraban altas variabilidades en las probabilidades a posteriori cuando se imputaba alguna variable del submodelo “Services”, lo que evidencia, que estas variables condicionan la intención de contratar servicios (“Services”), sobretodo en las franjas de edad de 30 a 51 años en pacientes con ingresos entre 3000€ y 4000€. (iv) En el nodo “Services” (submodelo) los pacientes de las clínicas dentales mostraron altas probabilidades a priori para contratar servicios de fisiotrapia oral y gingival: “Dental Health Education” y “Parking”. (v) Las variables de fidelidad del paciente medidas desde su perspectiva comportamental que fueron utilizadas en el modelo: “Visit/year” “Time_clinic”, no aportaron información significativa. Tampoco, la variable de fidelidad del cliente (actitudinal): “Churn Efford”. (vi) De las entrevistas realizadas a expertos dentistas se obtiene que, los propietarios de la clínica tradicional tienen poca disposición a implementar nuevas estrategias comerciales, debido a la falta de formación en la gestión comercial y por falta de recursos y herramientas. Existe un rechazo generalizado hacia los nuevos modelos de negocios de clínicas dentales, especialmente en las franquicias y en lo que a políticas comerciales se refiere. Esto evidencia una carencia de gerencia empresarial en el sector. Como líneas futuras de investigación, se propone profundizar en algunas relaciones de dependencia (causales) como SERVQUALServices; SatisfactionServices; RelationalMKServices, Perception of diseaseSatisfaction, entre otras. Así como, otras variables de medición de la fidelidad comportamental que contribuyan a la mejora del modelo, como por ej. Gasto del paciente y rentabilidad de la visita. ABSTRACT This doctoral dissertation proposes a model of the behavior of the dental-clinic customer, based on the service-quality perception (SERVQUAL), loyalty, Relational Marketing and some relevant socio-economical characteristics, of the dental-clinic customers. In particular, the field study has been developed in the geographical region of Madrid, Spain during the years 2012 and 2013. The first stage of the preparation of the model consist in the data gathering process. For this purpose, five interviews where realized to expert dentists and also two different types of surveys: one for the universe defined by the set of dental-clinic patients and the second for the universe defined by the set of the dentists of the dental clinics of the Madrid Community. A sample of 200 surveys where collected for patients and a sample of 220 surveys where collected from active dentists belonging to the Ilustre Colegio Oficial de Odontólogos y Estomatólogos de la I Región Madrid. In the second stage of the model preparation, the processes of data-analysis, induction and synthesis of the final model where performed. The Graphic Probabilistic Models methodology was used to elaborate the final model, specifically, a Bayesian Network, where the variables (nodes) and their statistical and causal dependencies where integrated and modeled, representing thus, the obtained knowledge from the data obtained by the surveys and the scientific knowledge derived from previous research in the field. A Bayesian Net consisting on six principal nodes was obtained, of which two of them are directly observable: “Revisit Intention” y “SERVQUAL”, and the remaining four are submodels (a grouping of variables). These are: “Attitudinal”, “Disease Information”, “Socioeconomical” and “Services”. The main conclusions derived from the model, as an inference tool, and the analysis of the interviews are: (i) the variables inside the “Attitudinal” node are the most sensitive and significant. By making some particular imputations on the variables that conform the “Attitudinal” node (“RelationalMk”, “Satisfaction”, “Recommendation” y “Friendship”), high posterior probabilities (measured in revisit intention) are obtained for the loyalty of the dental-clinic patient. (ii) In the “Disease Information” node, the causal relation between the “Perception of disease” and “SERVQUAL” when “Perception of disease” is imputed is highlighted, showing that the perception of the severity of the patient’s disease conditions significantly the perception of service quality. As an example, by imputing some particular values to the “Clinic_Type” node high posterior probabilities are obtained for the “SERVQUAL” variables and for “Revisit Intention” showing that the clinic type influences significantly in the service quality perception and loyalty (revisit intention). (iii) In the “Socioeconomical” variable, the variable “Sex” showed to be non-significant, however, the “Age” variable and “Income” show high variability in its posterior probabilities when some variable from the “Services” node where imputed, showing thus, that these variables condition the intention to buy new services (“Services”), especially in the age range from 30 to 50 years in patients with incomes between 3000€ and 4000€. (iv) In the “Services” submodel the dental-clinic patients show high priors to buy services such as oral and gingival therapy, Dental Health Education and “Parking” service. (v) The obtained loyalty measures, from the behavioral perspective, “Visit/year” and “Time_clinic”, do not add significant information to the model. Neither the attitudinal loyalty component “Churn Efford”. (vi) From the interviews realized to the expert dentists it is observed that the owners of the traditional clinics have a low propensity to apply new commercial strategies due to a lack of resources and tools. In general, there exists an opposition to new business models in the sector, especially to the franchise dental model. All of this evidences a lack in business management in the sector. As future lines of research, a deep look into some statistical and causal relations is proposed, such as: SERVQUALServices; SatisfactionServices; RelationalMKServices, Perception of diseaseSatisfaction, as well as new measurement variables related to attitudinal loyalty that contribute to improve the model, for example, profit per patient and per visit.

Motivación, flow e intención de práctica físico-deportiva en estudiantes de educación física de España y Latinoamérica

A pesar de los innegables beneficios físicos y psicosociales que la práctica de actividad física tiene para la población en las últimas décadas se observa un importante descenso en el nivel de práctica de actividad física durante la adolescencia. La Educación Física (EF) es una asignatura presente en las primeras etapas educativas de los currículums de todos los países y supone para la población infantil y adolescente, durante el periodo de escolarización obligatoria, un entorno de contacto cotidiano con la actividad física y deportiva lo que explica el creciente interés que existe por investigar en este contexto y extraer conclusiones que puedan ayudar a revertir el proceso de progresivo abandono de la práctica en estas edades. El presente trabajo se centra en un periodo, la adolescencia, especialmente sensible al abandono de la práctica de actividad física. Apoyándonos en tres de los marcos teóricos más importantes de los últimos años - Teoría de Metas de Logro, Teoría de la Autodeterminación y Teoría del Flow - hemos realizado un diseño con tres estudios complementarios que nos permitan avanzar en el conocimiento de las variables que afectan a esta realidad. En el primero de los estudios, en el que participaron 3990 estudiantes de EF de España, Argentina, Colombia y Ecuador con edades comprendidas entre 12 y 18 años, se fijaron como objetivos el establecimiento de perfiles motivacionales en estudiantes de EF considerando las orientaciones motivacionales, la motivación intrínseca y el flow disposicional; la comprobación de la posible estabilidad de los perfiles establecidos en cuatro países diferentes; y el análisis de la relación entre los perfiles motivacionales establecidos con la práctica de actividad física realizada en la actualidad y la intención de ser activo en el futuro. Los resultados revelaron la existencia de tres perfiles motivacionales en los estudiantes: perfil de motivación baja-moderada, perfil de motivación de alta motivación con bajo ego y perfil de alta motivación. Se encontraron similitudes en los perfiles motivacionales obtenidos en los cuatro países analizados, sugiriéndose la posibilidad de que la lengua materna compartida pueda ser una variable de influencia en la existencia de patrones conductuales similares. La orientación al ego resultó ser un elemento diferenciador en la relación de los dos perfiles que mostraron niveles más altos de motivación intrínseca, flow disposicional y orientación a la tarea con las variables de práctica. Mayores niveles de orientación al ego determinaron mayores valores de práctica e intención de práctica. En el segundo estudio, en el que participaron 365 estudiantes de EF de España, Argentina y Colombia con edades comprendidas entre 12 y 16 años, se testó un modelo explicativo de la intención de ser físicamente activo en el futuro en estudiantes de EF poco motivados introduciendo el flow disposicional como variable explicativa junto a las orientaciones motivacionales y la motivación intrínseca. El modelo de ecuaciones estructurales testado muestra que tanto la orientación al ego como la orientación a la tarea y la motivación intrínseca predijeron el flow disposicional. No se encontró un efecto significativo de la orientación a la tarea sobre la motivación intrínseca, ni de esta sobre la intención de práctica de AFD en el futuro. El flow disposicional resultó ser un mediador entre ambas orientaciones motivacionales y dicha intención, adquiriendo un papel relevante en la predicción de la intención de realizar actividad física en el futuro en los sujetos con poca motivación hacia la clase de EF. En el último estudio, con una muestra de 53 estudiantes de EF pertenecientes a dos clases de segundo curso de ESO con edades comprendidas entre 13 y 15 años, se analizó el efecto de una intervención de apoyo a las NPB sobre la satisfacción de las mismas, la motivación intrínseca, la disposición a experimentar flow y la intención de ser físicamente activo en el futuro; estudiándose también el efecto de la misma sobre ciertas variables presentes en el proceso de enseñanza-aprendizaje tales como la diversión, el aprendizaje y el gusto hacia el contenido y la metodología empleada. La intervención resultó efectiva en la mejora de todas las variables motivacionales analizadas a excepción de la satisfacción de la necesidad de relaciones sociales, variable que podría ser más difícilmente modificable en tanto que los grupos de clase suelen permanecer estables a lo largo de esta etapa educativa. Los alumnos de la condición experimental presentaron niveles más elevados de diversión, aprendizaje y gusto hacia el contenido y la metodología empleada. ABSTRACT Despite the undeniable physical and psychological benefits that physical activity has on health, a significant drop in the level of physical activity during adolescence has been observed over the last few decades. Physical education (PE) is present in the early stages of educational curricula of all countries, creating an environment in which children and adolescents can maintain daily contact with sport and physical activity during the period of compulsory education. There is thus a growing interest in research within this context, helping to draw conclusions aimed at reversing the progressive decline of physical activity in this age bracket. The work presented here focuses on adolescence – a period particularly sensitive when faced with declining rates of physical activity. Relying on three of the most important recent theoretical frameworks – Achievement Goal Theory, Self-Determination Theory and Flow Theory – we have carried out a design using three complementary studies that allow us to advance the understanding of variables affecting this reality. The first two studies employ a correlational methodology while the third follows a quasi-experimental design. The objectives of the first study, with the participation of 3990 PE students aged 12 to 18 from Spain, Argentina, Colombia and Ecuador, were: a) to establish motivational profiles in physical education students taking into consideration motivational orientations, intrinsic motivation and dispositional flow; b) to check the possible stability of the established profiles in the four countries; and c) to analyze the relationship between motivational profiles and both current levels of physical activity and intention to be physically active in the future. Results revealed the existence of three motivational profiles: low-moderate motivation profile, high motivation and low ego profile and high motivation profile. Similarities were found across the four countries, which presents the possibility that sharing the same mother tongue might influence the existence of similar behavioral patterns. Amongst the profiles that showed the highest levels of intrinsic motivation, dispositional flow and task orientation with practice variables, ego orientation became apparent as a differentiating element. Higher levels of ego orientation correlated with higher levels both in current level of physical activity and intention to be physically active in the future. In the second study, with the participation of 365 PE students aged 12 to 16 from Spain, Argentina and Colombia, an explanatory model of the intention to be physically active within the low-moderate motivation profile was tested, including dispositional flow as an influence variable together with motivational orientations and intrinsic motivation. The structural model equation in the low-moderate motivation profile shows some differences with respect to findings of similar studies using heterogeneous samples in motivational profiles. It was found that ego orientation, task orientation and intrinsic motivation predicted dispositional flow. No significant effects of task orientation on intrinsic motivation, or of intrinsic motivation on intention to be physically active in the future were found. Dispositional flow emerged as a mediator between both motivational orientations and intention, acquiring an important role in the prediction of future intentions to be physically active in adolescents who show low levels of motivation towards physical education. In the last of the three studies, with the participation of 53 PE students drawn from two classes in the second year of secondary education aged 13 to 15, the effect of an intervention to support basic psychological needs was tested against the satisfaction of these needs, intrinsic motivation, disposition to experience flow and intention to be physically active in the future. Alongside this, the aforementioned intervention was tested on certain variables present in the teaching-learning process such as fun, learning and taste for the activity and methodology. Supportive intervention was effective in improving all the motivational variables, except for the satisfaction of the relatedness variable, which may be more difficult to modify as class groups tend to remain stable throughout this educational state. Students in the experimental condition showed higher levels of fun, learning and taste for the content and methodology.

GESTÃO DO CONHECIMENTO: UM ESTUDO SOBRE A RELAÇÃO ENTRE A LIDERANÇA TRANSFORMACIONAL, A CONVERSÃO DO CONHECIMENTO E A EFICÁCIA ORGANIZACIONAL

Este estudo teve como objetivo principal analisar a relação entre a Liderança Transformacional, a Conversão do Conhecimento e a Eficácia Organizacional. Foram considerados como pressupostos teóricos conceitos consolidados sobre os temas desta relação, além de recentes pesquisas já realizadas em outros países e contextos organizacionais. Com base nisto identificou-se potencial estudo de um modelo que relacionasse estes três conceitos. Para tal considera-se que as organizações que buscam atingir Vantagem Competitiva e incorporam a Knowledge-Based View possam conquistar diferenciação frente a seus concorrentes. Nesse contexto o conhecimento ganha maior destaque e papel protagonista nestas organizações. Dessa forma criar conhecimento através de seus colaboradores, passa a ser um dos desafios dessas organizações ao passo que sugere melhoria de seus indicadores Econômicos, Sociais, Sistêmicos e Políticos, o que se define por Eficácia Organizacional. Portanto os modos de conversão do conhecimento nas organizações, demonstram relevância, uma vez que se cria e se converte conhecimentos através da interação entre o conhecimento existente de seus colaboradores. Essa conversão do conhecimento ou modelo SECI possui quatro modos que são a Socialização, Externalização, Combinação e Internalização. Nessa perspectiva a liderança nas organizações apresenta-se como um elemento capaz de influenciar seus colaboradores, propiciando maior dinâmica ao modelo SECI de conversão do conhecimento. Se identifica então na liderança do tipo Transformacional, características que possam influenciar colaboradores e entende-se que esta relação entre a Liderança Transformacional e a Conversão do Conhecimento possa ter influência positiva nos indicadores da Eficácia Organizacional. Dessa forma esta pesquisa buscou analisar um modelo que explorasse essa relação entre a liderança do tipo Transformacional, a Conversão do Conhecimento (SECI) e a Eficácia Organizacional. Esta pesquisa teve o caráter quantitativo com coleta de dados através do método survey, obtendo um total de 230 respondentes válidos de diferentes organizações. O instrumento de coleta de dados foi composto por afirmativas relativas ao modelo de relação pesquisado com um total de 44 itens. O perfil de respondentes concentrou-se entre 30 e 39 anos de idade, com a predominância de organizações privadas e de departamentos de TI/Telecom, Docência e Recursos Humanos respectivamente. O tratamento dos dados foi através da Análise Fatorial Exploratória e Modelagem de Equações Estruturais via Partial Least Square Path Modeling (PLS-PM). Como resultado da análise desta pesquisa, as hipóteses puderam ser confirmadas, concluindo que a Liderança Transformacional apresenta influência positiva nos modos de Conversão do Conhecimento e que; a Conversão do Conhecimento influencia positivamente na Eficácia Organizacional. Ainda, concluiu-se que a percepção entre os respondentes não apresenta resultado diferente sobre o modelo desta pesquisa entre quem possui ou não função de liderança.

Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease

Glial-cell-line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for adult nigral dopamine neurons in vivo. GDNF has both protective and restorative effects on the nigro-striatal dopaminergic (DA) system in animal models of Parkinson disease. Appropriate administration of this factor is essential for the success of its clinical application. Since it cannot cross the blood–brain barrier, a gene transfer method may be appropriate for delivery of the trophic factor to DA cells. We have constructed a recombinant adenovirus (Ad) encoding GDNF and injected it into rat striatum to make use of its ability to infect neurons and to be retrogradely transported by DA neurons. Ad-GDNF was found to drive production of large amounts of GDNF, as quantified by ELISA. The GDNF produced after gene transfer was biologically active: it increased the survival and differentiation of DA neurons in vitro. To test the efficacy of the Ad-mediated GDNF gene transfer in vivo, we used a progressive lesion model of Parkinson disease. Rats received injections unilaterally into their striatum first of Ad and then 6 days later of 6-hydroxydopamine. We found that mesencephalic nigral dopamine neurons of animals treated with the Ad-GDNF were protected, whereas those of animals treated with the Ad-β-galactosidase were not. This protection was associated with a difference in motor function: amphetamine-induced turning was much lower in animals that received the Ad-GDNF than in the animals that received Ad-β-galactosidase. This finding may have implications for the development of a treatment for Parkinson disease based on the use of neurotrophic factors.

Rapid down-regulation of mammalian Period genes during behavioral resetting of the circadian clock

The pervasive role of circadian clocks in regulating physiology and behavior is widely recognized. Their adaptive value is their ability to be entrained by environmental cues such that the internal circadian phase is a reliable predictor of solar time. In mammals, both light and nonphotic behavioral cues can entrain the principal oscillator of the hypothalamic suprachiasmatic nuclei (SCN). However, although light can advance or delay the clock during circadian night, behavioral events trigger phase advances during the subjective day, when the clock is insensitive to light. The recent identification of Period (Per) genes in mammals, homologues of dperiod, which encodes a core element of the circadian clockwork in Drosophila, now provides the opportunity to explain circadian timing and entrainment at a molecular level. In mice, expression of mPer1 and mPer2 in the SCN is rhythmic and acutely up-regulated by light. Moreover, the temporal relations between mRNA and protein cycles are consistent with a clock based on a transcriptional/translational feedback loop. Here we describe circadian oscillations of Per1 and Per2 in the SCN of the Syrian hamster, showing that PER1 protein and mRNA cycles again behave in a manner consistent with a negative-feedback oscillator. Furthermore, we demonstrate that nonphotic resetting has the opposite effect to light: acutely down-regulating these genes. Their sensitivity to nonphotic resetting cues supports their proposed role as core elements of the circadian oscillator. Moreover, this study provides an explanation at the molecular level for the contrasting but convergent effects of photic and nonphotic cues on the clock.

Orphanin FQ acts as an anxiolytic to attenuate behavioral responses to stress

Orphanin FQ (OFQ, Nociceptin) is a recently discovered 17-amino acid neuropeptide that is structurally related to the opioid peptides but does not bind opioid receptors. OFQ has been proposed to act as an anti-opioid peptide, but its widespread sites of action in the brain suggest that it may have more general functions. Here we show that OFQ plays an important role in higher brain functions because it can act as an anxiolytic to attenuate the behavioral inhibition of animals acutely exposed to stressful/anxiogenic environmental conditions. OFQ anxiolytic-like effects were consistent across several behavioral paradigms generating different types of anxiety states in animals (light-dark preference, elevated plus-maze, exploratory behavior of an unfamiliar environment, pharmacological anxiogenesis, operant conflict) and were observed at low nonsedating doses (0.1–3 nmol, intracerebroventricular). Like conventional anxiolytics, OFQ interfered with regular sensorimotor function at high doses (>3 nmol). Our results show that an important role of OFQ is to act as an endogenous regulator of acute anxiety responses. OFQ, probably in concert with other major neuropeptides, exerts a modulatory role on the central integration of stressful stimuli and, thereby, may modulate anxiety states generated by acute stress.

Elucidation of a PTS–Carbohydrate Chemotactic Signal Pathway in Escherichia coli Using a Time-resolved Behavioral Assay

Chemotaxis of Escherichia coli toward phosphotransferase systems (PTSs)–carbohydrates requires phosphoenolpyruvate-dependent PTSs as well as the chemotaxis response regulator CheY and its kinase, CheA. Responses initiated by flash photorelease of a PTS substrates d-glucose and its nonmetabolizable analog methyl α-d-glucopyranoside were measured with 33-ms time resolution using computer-assisted motion analysis. This, together with chemotactic mutants, has allowed us to map out and characterize the PTS chemotactic signal pathway. The responses were absent in mutants lacking the general PTS enzymes EI or HPr, elevated in PTS transport mutants, retarded in mutants lacking CheZ, a catalyst of CheY autodephosphorylation, and severely reduced in mutants with impaired methyl-accepting chemotaxis protein (MCP) signaling activity. Response kinetics were comparable to those triggered by MCP attractant ligands over most of the response range, the most rapid being 11.7 ± 3.1 s−1. The response threshold was <10 nM for glucose. Responses to methyl α-d-glucopyranoside had a higher threshold, commensurate with a lower PTS affinity, but were otherwise kinetically indistinguishable. These facts provide evidence for a single pathway in which the PTS chemotactic signal is relayed rapidly to MCP–CheW–CheA signaling complexes that effect subsequent amplification and slower CheY dephosphorylation. The high sensitivity indicates that this signal is generated by transport-induced dephosphorylation of the PTS rather than phosphoenolpyruvate consumption.

Behavioral alterations associated with apoptosis and down-regulation of presenilin 1 in the brains of p53-deficient mice

Presenilin 1 (PS1) expression is repressed by the p53 tumor suppressor. As shown herein, wild-type PS1 is an effective antiapoptotic molecule capable of significantly inhibiting p53-dependent and p53-independent cell death. We analyzed, at the functional and molecular levels, the brains of p53 knockout mice. Surprisingly, we found that lack of p53 expression induces apoptotic brain lesions, accompanied by learning deficiency and behavioral alterations. p53-deficient mice show an unexpected overexpression of p21waf1 with subsequent down-regulation of PS1 in their brains. This process is progressive and age-dependent. These data indicate that the p53 pathway, besides affecting tumor suppression, may play a major role in regulating neurobehavioral function and cell survival in the brain.

Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities

A mouse model for Down syndrome, Ts1Cje, has been developed. This model has made possible a step in the genetic dissection of the learning, behavioral, and neurological abnormalities associated with segmental trisomy for the region of mouse chromosome 16 homologous with the so-called “Down syndrome region” of human chromosome segment 21q22. Tests of learning in the Morris water maze and assessment of spontaneous locomotor activity reveal distinct learning and behavioral abnormalities, some of which are indicative of hippocampal dysfunction. The triplicated region in Ts1Cje, from Sod1 to Mx1, is smaller than that in Ts65Dn, another segmental trisomy 16 mouse, and the learning deficits in Ts1Cje are less severe than those in Ts65Dn. In addition, degeneration of basal forebrain cholinergic neurons, which was observed in Ts65Dn, was absent in Ts1Cje.