Structural basis for receptor subtype-specific regulation revealed by a chimeric beta 3/beta 2-adrenergic receptor.

The physiological significance of multiple G-protein-coupled receptor subtypes, such as the beta-adrenergic receptors (beta ARs), remains obscure, since in many cases several subtypes activate the same effector and utilize the same physiological agonists. We inspected the deduced amino acid sequences of the beta AR subtypes for variations in the determinants for agonist regulation as a potential basis for subtype differentiation. Whereas the beta 2AR has a C terminus containing 11 serine and threonine residues representing potential sites for beta AR kinase phosphorylation, which mediates rapid agonist-promoted desensitization, only 3 serines are present in the comparable region of the beta 3AR, and they are in a nonfavorable context. The beta 3AR also lacks sequence homology in regions which are important for agonist-mediated sequestration and down-regulation of the beta 2AR, although such determinants are less well defined. We therefore tested the idea that the agonist-induced regulatory properties of the two receptors might differ by expressing both subtypes in CHW cells and exposing them to the agonist isoproterenol. The beta 3AR did not display short-term agonist-promoted functional desensitization or sequestration, or long-term down-regulation. To assign a structural basis for these subtype-specific differences in agonist regulation, we constructed a chimeric beta 3/beta 2AR which comprised the beta 3AR up to proline-365 of the cytoplasmic tail and the C terminus of the beta 2AR. When cells expressing this chimeric beta 3/beta 2AR were exposed to isoproterenol, functional desensitization was observed. Whole-cell phosphorylation studies showed that the beta 2AR displayed agonist-dependent phosphorylation, but no such phosphorylation could be demonstrated with the beta 3AR, even when beta AR kinase was overexpressed. In contrast, the chimeric beta 3/beta 2AR did display agonist-dependent phosphorylation, consistent with its functional desensitization. In addition to conferring functional desensitization and phosphorylation to the beta 3AR, the C-terminal tail of the beta 2AR also conferred agonist-promoted sequestration and long-term receptor down-regulation.

Weight loss intervention for young adults using mobile technology: design and rationale of a randomized controlled trial - Cell Phone Intervention for You (CITY).

BACKGROUND: The obesity epidemic has spread to young adults, leading to significant public health implications later in adulthood. Intervention in early adulthood may be an effective public health strategy for reducing the long-term health impact of the epidemic. Few weight loss trials have been conducted in young adults. It is unclear what weight loss strategies are beneficial in this population. PURPOSE: To describe the design and rationale of the NHLBI-sponsored Cell Phone Intervention for You (CITY) study, which is a single center, randomized three-arm trial that compares the impact on weight loss of 1) a behavioral intervention that is delivered almost entirely via cell phone technology (Cell Phone group); and 2) a behavioral intervention delivered mainly through monthly personal coaching calls enhanced by self-monitoring via cell phone (Personal Coaching group), each compared to 3) a usual care, advice-only control condition. METHODS: A total of 365 community-dwelling overweight/obese adults aged 18-35 years were randomized to receive one of these three interventions for 24 months in parallel group design. Study personnel assessing outcomes were blinded to group assignment. The primary outcome is weight change at 24 [corrected] months. We hypothesize that each active intervention will cause more weight loss than the usual care condition. Study completion is anticipated in 2014. CONCLUSIONS: If effective, implementation of the CITY interventions could mitigate the alarming rates of obesity in young adults through promotion of weight loss. ClinicalTrial.gov: NCT01092364.

Adaptive intervention design in mobile health: Intervention design and development in the Cell Phone Intervention for You trial.

BACKGROUND/AIMS: The obesity epidemic has spread to young adults, and obesity is a significant risk factor for cardiovascular disease. The prominence and increasing functionality of mobile phones may provide an opportunity to deliver longitudinal and scalable weight management interventions in young adults. The aim of this article is to describe the design and development of the intervention tested in the Cell Phone Intervention for You study and to highlight the importance of adaptive intervention design that made it possible. The Cell Phone Intervention for You study was a National Heart, Lung, and Blood Institute-sponsored, controlled, 24-month randomized clinical trial comparing two active interventions to a usual-care control group. Participants were 365 overweight or obese (body mass index≥25 kg/m2) young adults. METHODS: Both active interventions were designed based on social cognitive theory and incorporated techniques for behavioral self-management and motivational enhancement. Initial intervention development occurred during a 1-year formative phase utilizing focus groups and iterative, participatory design. During the intervention testing, adaptive intervention design, where an intervention is updated or extended throughout a trial while assuring the delivery of exactly the same intervention to each cohort, was employed. The adaptive intervention design strategy distributed technical work and allowed introduction of novel components in phases intended to help promote and sustain participant engagement. Adaptive intervention design was made possible by exploiting the mobile phone's remote data capabilities so that adoption of particular application components could be continuously monitored and components subsequently added or updated remotely. RESULTS: The cell phone intervention was delivered almost entirely via cell phone and was always-present, proactive, and interactive-providing passive and active reminders, frequent opportunities for knowledge dissemination, and multiple tools for self-tracking and receiving tailored feedback. The intervention changed over 2 years to promote and sustain engagement. The personal coaching intervention, alternatively, was primarily personal coaching with trained coaches based on a proven intervention, enhanced with a mobile application, but where all interactions with the technology were participant-initiated. CONCLUSION: The complexity and length of the technology-based randomized clinical trial created challenges in engagement and technology adaptation, which were generally discovered using novel remote monitoring technology and addressed using the adaptive intervention design. Investigators should plan to develop tools and procedures that explicitly support continuous remote monitoring of interventions to support adaptive intervention design in long-term, technology-based studies, as well as developing the interventions themselves.

Lactancias extendidas en sistemas de producción lechera argentinos

En la Argentina los sistemas de producción de leche utilizan animales mejorados genéticamente para producir en condiciones de dietas muy suplementadas en planteos productivos de base pastoril con suplementación. En estos sistemas el objetivo es obtener un parto por vaca por año pero son muy pocos los tambos que llegan a cumplirlo porque se atrasa el momento de la concepción prolongando las lactancias. El objetivo del trabajo fue investigar los factores que influyen en la productividad de tambos ubicados en el centro de la provincia de Santa Fe y las razones que determinan la duración de las lactancias en estos tambos con el fin de analizar estrategias de manejo que consideren el uso de lactancias extendidas para lograr aumentos de productividad sostenibles. Adicionalmente se exploraron aquellos factores reproductivos asociados al largo de lactancia, como determinante de los litros totales producidos por vaca. Se analizó información de 1620 vacas de once tambos, recolectada en junio de 2008. Para cada tambo y para el conjunto de tambos se estimaron los valores promedio y desvío estándar del porcentaje de vacas secadas antes de los 365 días en lactancia (DEL), porcentaje de vacas vacías con más de 200 DEL y los servicios por vaca hasta confirmar preñez. En las vacas que cerraron su lactancia durante el periodo julio 2007 - junio 2008 (n igual a 892) se estimó la producción de leche acumulada al fin de la lactancia (PT), la producción de leche diaria (PD) y el valor de DEL. Además se estimó la producción de leche por hectárea y la carga animal. Los datos se analizaron por regresión lineal. Para explorar la relación entre PT con PD y DEL se hizo un análisis de regresión múltiple. En los casos analizados el aumento en la duración de la lactancia sería consecuencia de un atraso en el logro de preñez con un impacto relativamente bajo sobre la productividad de los sistemas.

Worksheet for astronomical variables (VARAST 1.0)

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Relaciones suelo planta de crisantemos (Dendranthema grandiflora) en maceta

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Worksheet for astronomical variables (VARAST 1.0)

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Algunas dificultades que presentan los estudiantes al asociar ecuaciones lineales con su representación gráfica

Frecuentemente, se hace énfasis en la enseñanza y aprendizaje de las matemáticas movilizar diversos registros de representación de una misma gestión. Sin embargo, el tratamiento de conversión de una representación en una representación de otro registro no es fácil y en ocasiones hasta imposible. Al respecto, Duval (1988) señala: “cuando se efectúa la conversión ecuación → gráfico no surge ninguna dificultad, pero todo cambia cuando se hace la conversión inversa”. Este aporte es muy sobresaliente e induce a investigar la naturaleza de esta problemática. En este sentido, nuestro trabajo de investigación está enfocado en identificar algunas dificultades que puedan presentar los estudiantes al tratar de poner en correspondencia el registro gráfico con el algebraico. Para ello, se aplicaron actividades donde se exponen algunos valores visuales de la gráfica, con el fin de establecer una correspondencia entre esos valores visuales de la recta y su respectiva escritura algebraica, así como, establecer un sistema para las diferentes categorías de tres rectas en el plano.