Antiproliferative Role of Dopamine: Loss of D2 Receptors Causes Hormonal Dysfunction and Pituitary Hyperplasia

AbstractThe function of dopamine (DA) in the nervous system is paralleled by its neuroendocrine control of pituitary gland functions. Here, we document the neuroendocrine function of dopamine by studying the pituitary gland of mice lacking DA D2 receptors (D2R). These mice present a striking, progressive increase in lactotroph number, which ultimately leads to tumors in aged animals. Females develop tumors much earlier than males. An estrogen-mediated lactotroph proliferation cannot account for this sexual dimorphism, since D2R-null females are hypoestrogenic and, thus, have estrogen levels similar to males. In contrast, prolactin levels are six times higher in females than in males. We show that active prolactin receptors are present in the pituitary and their expression increases in concomitance with tumor expansion. These results point to prolactin as an autocrine proliferative factor in the pituitary gland. Additionally, they demonstrate an antiproliferative function for DA regulated through D2 receptor activation

Sistema lidar heterodino para medida de desplazamiento de superficies

Presentamos un prototipo de un sistema lidar (radar láser) de onda continua heterodino de baja potencia, para la medida de la velocidad de desplazamiento de superficies. Ofrece simplicidad y fácil alineación de todos los dispositivos ópticos. Permite medir la velocidad de blancos a distancias de más de 6 m y, empleando una frecuencia intermedia de 160MHz, obtener información del signo de la velocidad. Esta frecuencia intermedia se consigue mediante la inserción de un modulador acusto óptico (AOM). La detección se real iza sobre la superficie activa de un fotodiodo de avalancha (APD). En este artículo presentamos la descripción del sistema y medidas de laboratorio de potencia, anchura espectral y tolerancia en distancia.Peer ReviewedPostprint (published version

Non-CO2 generating energy shares in the world : cross-country differences and polarization.

The aim of this paper is to examine the spatial distribution of non-CO2 generating energy sources in the world for the period 1990–2009, paying special attention to the evolution of cross-country disparities. To this end, after carrying out a classical convergence analysis, a more thorough investigation of the entire distribution is presented by examining its external shape, the intra-distribution dynamics and the long-run equilibrium distribution. This analysis reveals the existence of a weak, rather insignificant, convergence process and that large crosscountry differences are likely to persist in the long-run. Next, as polarization indicators are a proper way of appraising potential conflict in international environmental negotiations, we test whether, or not, the distribution dynamics concurs with the presence of polarization. Our results indicate that two poles can be clearly differentiated, one with high and other with low non-CO2 generating energy shares. In view of these findings, and to ensure a fair transition to a sustainable energy system, the paper calls for the development of an ambitious clean energy agenda, especially in countries with low non-CO2 generating energy shares

Attention modulates adaptive motor learning in the ‘broken escalator’ paradigm

The physical stumble caused by stepping onto a stationary (broken) escalator represents a locomotor aftereffect (LAE) that attests to a process of adaptive motor learning. Whether such learning is primarily explicit (requiring attention resources) or implicit (independent of attention) is unknown. To address this question, we diverted attention in the adaptation (MOVING) and aftereffect (AFTER) phases of the LAE by loading these phases with a secondary cognitive task (sequential naming of a vegetable, fruit and a colour). Thirty-six healthy adults were randomly assigned to 3 equally sized groups. They performed 5 trials stepping onto a stationary sled (BEFORE), 5 with the sled moving (MOVING) and 5 with the sled stationary again (AFTER). A 'Dual-Task-MOVING (DTM)' group performed the dual-task in the MOVING phase and the 'Dual-Task-AFTEREFFECT (DTAE)' group in the AFTER phase. The 'control' group performed no dual task. We recorded trunk displacement, gait velocity and gastrocnemius muscle EMG of the left (leading) leg. The DTM, but not the DTAE group, had larger trunk displacement during the MOVING phase, and a smaller trunk displacement aftereffect compared with controls. Gait velocity was unaffected by the secondary cognitive task in either group. Thus, adaptive locomotor learning involves explicit learning, whereas the expression of the aftereffect is automatic (implicit). During rehabilitation, patients should be actively encouraged to maintain maximal attention when learning new or challenging locomotor tasks

Quantifying geocode location error using GIS methods

BACKGROUND: The Metropolitan Atlanta Congenital Defects Program (MACDP) collects maternal address information at the time of delivery for infants and fetuses with birth defects. These addresses have been geocoded by two independent agencies: (1) the Georgia Division of Public Health Office of Health Information and Policy (OHIP) and (2) a commercial vendor. Geographic information system (GIS) methods were used to quantify uncertainty in the two sets of geocodes using orthoimagery and tax parcel datasets. METHODS: We sampled 599 infants and fetuses with birth defects delivered during 1994–2002 with maternal residence in either Fulton or Gwinnett County. Tax parcel datasets were obtained from the tax assessor's offices of Fulton and Gwinnett County. High-resolution orthoimagery for these counties was acquired from the U.S. Geological Survey. For each of the 599 addresses we attempted to locate the tax parcel corresponding to the maternal address. If the tax parcel was identified the distance and the angle between the geocode and the residence were calculated. We used simulated data to characterize the impact of geocode location error. In each county 5,000 geocodes were generated and assigned their corresponding Census 2000 tract. Each geocode was then displaced at a random angle by a random distance drawn from the distribution of observed geocode location errors. The census tract of the displaced geocode was determined. We repeated this process 5,000 times and report the percentage of geocodes that resolved into incorrect census tracts. RESULTS: Median location error was less than 100 meters for both OHIP and commercial vendor geocodes; the distribution of angles appeared uniform. Median location error was approximately 35% larger in Gwinnett (a suburban county) relative to Fulton (a county with urban and suburban areas). Location error occasionally caused the simulated geocodes to be displaced into incorrect census tracts; the median percentage of geocodes resolving into incorrect census tracts ranged between 4.5% and 5.3%, depending upon the county and geocoding agency. CONCLUSION: Geocode location uncertainty can be estimated using tax parcel databases in a GIS. This approach is a viable alternative to global positioning system field validation of geocodes

Baseline observations from the POSSIBLE EU® study: characteristics of postmenopausal women receiving bone loss medications

Summary: Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) is an ongoing longitudinal cohort study that utilises physician- and patient-reported measures to describe the characteristics and management of postmenopausal women on bone loss therapies. We report the study design and baseline characteristics of 3,402 women recruited from general practice across five European countries. Purpose The POSSIBLE EU® is a study describing the characteristics and management of postmenopausal women receiving bone loss medications. Methods: Between 2005 and 2008, general practitioners enrolled postmenopausal women initiating, switching or continuing treatment with bone loss treatment in France, Germany, Italy, Spain and the UK. Patients and physicians completed questionnaires at study entry and at 3-month intervals, for 1 year. Results: Of 3,402 women enrolled (mean age 68.2 years [SD] 9.83), 96% were diagnosed with low bone mass; 55% of these using dual energy X-ray absorptiometry. Most women (92%) had comorbidities. Mean minimum T score (hip or spine) at diagnosis was −2.7 (SD 0.89; median −2.7 [interquartile range, −3.2, −2.2]) indicating low bone mineral density. Almost 40% of the women had prior fractures in adulthood, mostly non-vertebral, non-hip in nature, 30% of whom had at least two fractures and more than half experienced moderate/severe pain or fatigue. Bisphosphonates were the most common type of bone loss treatment prescribed in the 12 months preceding the study. Conclusions POSSIBLE EU® characterises postmenopausal women with low bone mass, exhibiting a high rate of prevalent fracture, substantial bone fragility and overall comorbidity burden. Clinical strategies for managing osteoporosis in this population varied across the five participating European countries, reflecting their different guidelines, regulations and standards of care

A Virus-Encoded Cell–Cell Fusion Machine Dependent on Surrogate Adhesins

The reovirus fusion-associated small transmembrane (FAST) proteins function as virus-encoded cellular fusogens, mediating efficient cell–cell rather than virus–cell membrane fusion. With ectodomains of only ∼20–40 residues, it is unclear how such diminutive viral fusion proteins mediate the initial stages (i.e. membrane contact and close membrane apposition) of the fusion reaction that precede actual membrane merger. We now show that the FAST proteins lack specific receptor-binding activity, and in their natural biological context of promoting cell–cell fusion, rely on cadherins to promote close membrane apposition. The FAST proteins, however, are not specifically reliant on cadherin engagement to mediate membrane apposition as indicated by their ability to efficiently utilize other adhesins in the fusion reaction. Results further indicate that surrogate adhesion proteins that bridge membranes as close as 13 nm apart enhance FAST protein-induced cell–cell fusion, but active actin remodelling is required for maximal fusion activity. The FAST proteins are the first example of membrane fusion proteins that have specifically evolved to function as opportunistic fusogens, designed to exploit and convert naturally occurring adhesion sites into fusion sites. The capacity of surrogate, non-cognate adhesins and active actin remodelling to enhance the cell–cell fusion activity of the FAST proteins are features perfectly suited to the structural and functional evolution of these fusogens as the minimal fusion component of a virus-encoded cellular fusion machine. These results also provide a basis for reconciling the rudimentary structure of the FAST proteins with their capacity to fuse cellular membranes

Biochemical indices and life traits of loggerhead turtles (Caretta caretta) from Cape Verde Islands

The loggerhead turtle (Caretta caretta) is an endangered marine reptile for whom assessing population health requires knowledge of demographic parameters such as individual growth rate. In Cape Verde, as within several populations, adult female loggerhead sea turtles show a size-related behavioral and trophic dichotomy. While smaller females are associated with oceanic habitats, larger females tend to feed in neritic habitats, which is reflected in their physiological condition and in their offspring. The ratio of RNA/DNA provides a measure of cellular protein synthesis capacity, which varies depending on changes in environmental conditions such as temperature and food availability. The purpose of this study was to evaluate the combined use of morphometric data and biochemical indices as predictors of the physiological condition of the females of distinct sizes and hatchlings during their nesting season and how temperature may influence the physiological condition on the offspring. Here we employed biochemical indices based on nucleic acid derived indices (standardized RNA/DNA ratio-sRD, RNA concentration and DNA concentration) in skin tissue as a potential predictor of recent growth rate in nesting females and hatchling loggerhead turtles. Our major findings were that the physiological condition of all nesting females (sRD) decreased during the nesting season, but that females associated with neritic habitats had a higher physiological condition than females associated with oceanic habitats. In addition, the amount of time required for a hatchling to right itself was negatively correlated with its physiological condition (sRD) and shaded nests produced hatchlings with lower sRD. Overall, our results showed that nucleic acid concentrations and ratios of RNA to DNA are an important tool as potential biomarkers of recent growth in marine turtles. Hence, as biochemical indices of instantaneous growth are likely temperature-, size- and age-dependent, the utility and validation of these indices on marine turtles stocks deserves further study.The authors thank the Cape Verde Ministry of Environment (General Direction for the Environment), INDP (National Fisheries Institution), the Canary Islands Government (D.G. Africa and D.G. Research and Universities), ICCM (Canarian Institution for Marine Sciences), the Andalusian Government (Andalusian Environmental Office) and AEGINA PROJECT (INTERREG IIIB) for funding and hosting them during this study. The authors also thank the European Regional Development Fund (ERDF) through the COMPETE - Operational Competitiveness Programme, and national funds through FCT - PEst-C/MAR/LA0015/2011 for supporting the biochemical analysis

When, where and how osteoporosis-associated fractures occur: An analysis from the global longitudinal study of osteoporosis in women (GLOW)

Objective: To examine when, where and how fractures occur in postmenopausal women. Methods: We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3. Results: Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68-86% of NHNV and 68-83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling. Conclusion: In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year. © 2013 Costa et al

Primary versus secondary source of data in observational studies and heterogeneity in meta-analyses of drug effects: a survey of major medical journals

The data from individual observational studies included in meta-analyses of drug effects are collected either from ad hoc methods (i.e. "primary data") or databases that were established for non-research purposes (i.e. "secondary data"). The use of secondary sources may be prone to measurement bias and confounding due to over-the-counter and out-of-pocket drug consumption, or non-adherence to treatment. In fact, it has been noted that failing to consider the origin of the data as a potential cause of heterogeneity may change the conclusions of a meta-analysis. We aimed to assess to what extent the origin of data is explored as a source of heterogeneity in meta-analyses of observational studies.publishe