Identification of a third distinct estrogen receptor and reclassification of estrogen receptors in teleosts

This paper describes three distinct estrogen receptor (ER) subtypes: ERα, ERβ, and a unique type, ERγ, cloned from a teleost fish, the Atlantic croaker Micropogonias undulatus; the first identification of a third type of classical ER in vertebrate species. Phylogenetic analysis shows that ERγ arose through gene duplication from ERβ early in the teleost lineage and indicates that ERγ is present in other teleosts, although it has not been recognized as such. The Atlantic croaker ERγ shows amino acid differences in regions important for ligand binding and receptor activation that are conserved in all other ERγs. The three ER subtypes are genetically distinct and have different distribution patterns in Atlantic croaker tissues. In addition, ERβ and ERγ fusion proteins can each bind estradiol-17β with high affinity. The presence of three functional ERs in one species expands the role of ER multiplicity in estrogen signaling systems and provides a unique opportunity to investigate the dynamics and mechanisms of ER evolution.

Generation and reproductive phenotypes of mice lacking estrogen receptor β

Estrogens influence the differentiation and maintenance of reproductive tissues and affect lipid metabolism and bone remodeling. Two estrogen receptors (ERs) have been identified to date, ERα and ERβ. We previously generated and studied knockout mice lacking estrogen receptor α and reported severe reproductive and behavioral phenotypes including complete infertility of both male and female mice and absence of breast tissue development. Here we describe the generation of mice lacking estrogen receptor β (ERβ −/−) by insertion of a neomycin resistance gene into exon 3 of the coding gene by using homologous recombination in embryonic stem cells. Mice lacking this receptor develop normally and are indistinguishable grossly and histologically as young adults from their littermates. RNA analysis and immunocytochemistry show that tissues from ERβ −/− mice lack normal ERβ RNA and protein. Breeding experiments with young, sexually mature females show that they are fertile and exhibit normal sexual behavior, but have fewer and smaller litters than wild-type mice. Superovulation experiments indicate that this reduction in fertility is the result of reduced ovarian efficiency. The mutant females have normal breast development and lactate normally. Young, sexually mature male mice show no overt abnormalities and reproduce normally. Older mutant males display signs of prostate and bladder hyperplasia. Our results indicate that ERβ is essential for normal ovulation efficiency but is not essential for female or male sexual differentiation, fertility, or lactation. Future experiments are required to determine the role of ERβ in bone and cardiovascular homeostasis.

Estrogen receptor α, not β, is a critical link in estradiol-mediated protection against brain injury

Estradiol protects against brain injury, neurodegeneration, and cognitive decline. Our previous work demonstrates that physiological levels of estradiol protect against stroke injury and that this protection may be mediated through receptor-dependent alterations of gene expression. In this report, we tested the hypothesis that estrogen receptors play a pivotal role in mediating neuroprotective actions of estradiol and dissected the potential biological roles of each estrogen receptor (ER) subtype, ERα and ERβ, in the injured brain. To investigate and delineate these mechanisms, we used ERα-knockout (ERαKO) and ERβ-knockout (ERβKO) mice in an animal model of stroke. We performed our studies by using a controlled endocrine paradigm, because endogenous levels of estradiol differ dramatically among ERαKO, ERβKO, and wild-type mice. We ovariectomized ERαKO, ERβKO, and the respective wild-type mice and implanted them with capsules filled with oil (vehicle) or a dose of 17β-estradiol that produces physiological hormone levels in serum. One week later, mice underwent ischemia. Our results demonstrate that deletion of ERα completely abolishes the protective actions of estradiol in all regions of the brain; whereas the ability of estradiol to protect against brain injury is totally preserved in the absence of ERβ. Thus, our results clearly establish that the ERα subtype is a critical mechanistic link in mediating the protective effects of physiological levels of estradiol in brain injury. Our discovery that ERα mediates protection of the brain carries far-reaching implications for the selective targeting of ERs in the treatment and prevention of neural dysfunction associated with normal aging or brain injury.

Thyroid hormone and estrogen interact to regulate behavior.

Environmental perturbations that increase plasma thyroid hormone (T3) concentrations also profoundly affect female reproductive behavior and physiology. We explored whether these effects were mediated by interactions between T3 receptor (TR) and estrogen receptor (ER). This hypothesis was of interest because the half-site of a consensus T3 response element DNA sequence is identical to an ER response element (ERE), and TRs bind to a consensus ERE. Molecular data presented in the accompanying paper [Zhu, Y.-S., Yen, P.M., Chin, W.W.& Pfaff, D.W. (1996) Proc. Natl. Acad. Sci. USA 93, 12587-12592] demonstrate that TRs and ERs are both present in rat hypothalamic nuclear extracts and that both can bind to the promoter the hypothalamic gene preproenkephalin and that interations between liganded TRs and ERs affect preproenkephalin transcription. In this paper, we show that molecular interactions between TRs and ERs are sufficient to mediate environmental effects on estrogen-controlled reproductive behavior. Ovariectomized (OVX) rats treated with high doses of T3 showed significantly lower levels of lordosis behavior in response to estradiol benzoate (EB) compared with OVX females treated with EB alone. Conversely, thyroidectomized/OVX females treated with EB showed significantly greater levels of lordosis behavior compared with OVX females treated with EB, showing the effect of endogenous T3. Thyroid hormone interference with EB-induced behavior could not be explained by a reduction in plasma E2 concentrations or by a general reduction in responsiveness of EB-sensitive tissues. Moreover, numbers of hypothalamic ER-immunoreactive cells increased dramatically following T3 treatment. These data suggest that T3 may reduce EB-dependent sexual behavior through interactions between TR and ER in the nuclei of behaviorally relevant hypothalamic neurons, envisioning for the first time a functional consequence of interactions between two nuclear hormone receptors in brain. These results also open up the possibility of molecular interactions on DNA encoding environmental signals, a new field for the study of neuronal integration.

Efeito do inibidor de proteinase de origem vegetal EcTI, sobre a inflamação pulmonar alérgica crônica em camundongos Balb/c

INTRODUÇÃO: A prevalência de asma tem crescido e a maioria dos pacientes com asma grave não obtém o controle total dos sintomas com as terapias disponíveis, fazendo-se necessária a busca por novas alternativas terapêuticas. Inibidores de proteinases têm sido estudados como tratamento de processos inflamatórios, dentre eles o Enterolobium contortisiliquum Tripsin Inhibitor (EcTI) OBJETIVO: Avaliar se o inibidor de proteinase EcTI modula a hiperresponsividade brônquica à metacolina, inflamação, remodelamento e estresse oxidativo nas vias aéreas e septos alveolares em um modelo experimental de inflamação pulmonar alérgica crônica. MÉTODOS: Vinte e quatro camundongos Balb/c machos, entre seis e sete semanas de vida, pesando em media 25 g foram divididos em quatro grupos: C (controle), OVA (sensibilizados com ovalbumina, 50 ug intraperironeal (i.p) nos dias 0 e 14 e desafiados nos dias 22, 24, 26, 28); C+EC (controle tratados com EcTI (2 mg/kg/i.p) nos dias 22 a 28); OVA+EC (sensibilizados e desafiados com ovalbumina e também tratados com EcTI (2 mg/kg -i.p) nos dias 22 a 28). No dia 29, foram realizadas realizadas: (i) hiperresponsividade à metacolina e obtidas as respostas máximas de resistência e elastância do sistema respiratório; (ii) análise histopatológica do pulmão para quantificação de eosinófilos, fibras colágenas e elásticas nas vias aéreas (VA) e nos septos alveolares (SA); e (iii) imunohistoquímica para quantificação de células positivas para IFN-y, IL-4, IL-5, IL-13, MMP-9, TIMP-1, TGF-beta, iNOS, NF-kB e fração de volume de isoprostano nas VA e nos SA. Uma semana após o dia 29 foi realizada a técnica de anafilaxia cutanea passiva(PCA) para quantificar IgE e IgG1. A significância foi considerada quando p < 0,05. RESULTADOS: Houve aumento de todos os parâmetros avaliados no grupo OVA em relação ao grupo controle (p < 0,05). Houve atenuação da resposta máxima de Rrs e Ers no grupo OVA+EC comparado as grupo OVA (p < 0,05). O tratamento com EcTI nos animais sensibilizados atenuou o número de eosinófilos, células positivas para IL-4, IL-5, IL-13,IFN-y, iNOS, MMP-9, TIMP-1, NF-kB e TGF-beta e fração de volume de isoprostano, fibras colágenas e elásticas nas vias aéreas e nos séptos alveolares quando comparado ao grupo OVA (p < 0,05).Houve reaçao de PCA nos animais sensibilizados com ovalbumina. CONCLUSÃO: EcTI atenuou a hiperresponsividade brônquica, a inflamação, o remodelamento e o estresse oxidativo nesse modelo experimental de inflamação pulmonar alérgica crônica. Embora sejam necessários mais estudos, esse inibidor pode ser considerado uma futura ferramenta farmacológica para o tratamento de asma

On the steric and mass-induced contributions to the annual sea level variations in the Mediterranean Sea

The sea level variation (SLVtotal) is the sum of two major contributions: steric and mass-induced. The steric SLVsteric is that resulting from the thermal and salinity changes in a given water column. It only involves volume change, hence has no gravitational effect. The mass-induced SLVmass, on the other hand, arises from adding or subtracting water mass to or from the water column and has direct gravitational signature. We examine the closure of the seasonal SLV budget and estimate the relative importance of the two contributions in the Mediterranean Sea as a function of time. We use ocean altimetry data (from TOPEX/Poseidon, Jason 1, ERS, and ENVISAT missions) to estimate SLVtotal, temperature, and salinity data (from the Estimating the Circulation and Climate of the Ocean ocean model) to estimate SLVsteric, and time variable gravity data (from Gravity Recovery and Climate Experiment (GRACE) Project, April 2002 to July 2004) to estimate SLVmass. We find that the annual cycle of SLVtotal in the Mediterranean is mainly driven by SLVsteric but moderately offset by SLVmass. The agreement between the seasonal SLVmass estimations from SLVtotal – SLVsteric and from GRACE is quite remarkable; the annual cycle reaches the maximum value in mid-February, almost half a cycle later than SLVtotal or SLVsteric, which peak by mid-October and mid-September, respectively. Thus, when sea level is rising (falling), the Mediterranean Sea is actually losing (gaining) mass. Furthermore, as SLVmass is balanced by vertical (precipitation minus evaporation, P–E) and horizontal (exchange of water with the Atlantic, Black Sea, and river runoff) mass fluxes, we compared it with the P–E determined from meteorological data to estimate the annual cycle of the horizontal flux.

Vertical crustal motion along the Mediterranean and Black Sea coast derived from ocean altimetry and tide gauge data

Tide gauge (TG) data along the northern Mediterranean and Black Sea coasts are compared to the sea-surface height (SSH) anomaly obtained from ocean altimetry (TOPEX/Poseidon and ERS-1/2) for a period of nine years (1993–2001). The TG measures the SSH relative to the ground whereas the altimetry does so with respect to the geocentric reference frame; therefore their difference would be in principle a vertical ground motion of the TG sites, though there are different error sources for this estimate as is discussed in the paper. In this study we estimate such vertical ground motion, for each TG site, from the slope of the SSH time series of the (non-seasonal) difference between the TG record and the altimetry measurement at a point closest to the TG. Where possible, these estimates are further compared with those derived from nearby continuous Global Positioning System (GPS) data series. These results on vertical ground motion along the Mediterranean and Black Sea coasts provide useful source data for studying, contrasting, and constraining tectonic models of the region. For example, in the eastern coast of the Adriatic Sea and in the western coast of Greece, a general subsidence is observed which may be related to the Adriatic lithosphere subducting beneath the Eurasian plate along the Dinarides fault.

Relationship between piezometric level and ground deformations measured by means of DInSAR in the Vega Media of the Segura River (Spain)

Differential SAR Interferometry (DInSAR) is a remote sensing method with the well demonstrated ability to monitor geological hazards like earthquakes, landslides and subsidence. Among all these hazards, subsidence involves the settlement of the ground surface affecting wide areas. Frequently, subsidence is induced by overexploitation of aquifers and constitutes a common problem that affects developed societies. The excessive pumping of underground water decreases the piezometric level in the subsoil and, as a consequence, increases the effective stresses with depth causing a consolidation of the soil column. This consolidation originates a settlement of ground surface that must be withstood by civil structures built on these areas. In this paper we make use of an advanced DInSAR approach - the Coherent Pixels Technique (CPT) [1] - to monitor subsidence induced by aquifer overexploitation in the Vega Media of the Segura River (SE Spain) from 1993 to the present. 28 ERS-1/2 scenes covering a time interval of about 10 years were used to study this phenomenon. The deformation map retrieved with CPT technique shows settlements of up to 80 mm at some points of the studied zone. These values agree with data obtained by means of borehole extensometers, but not with the distribution of damaged buildings, well points and basements, because the occurrence of damages also depends on the structural quality of the buildings and their foundations. The most interesting relationship observed is the one existing between piezometric changes, settlement evolution and local geology. Three main patterns of ground surface and piezometric level behaviour have been distinguished for the study zone during this period: 1) areas where deformation occurs while ground conditions remain altered (recent deformable sediments), 2) areas with no deformation (old and non-deformable materials), and 3) areas where ground deformation mimics piezometric level changes (expansive soils). The temporal relationship between deformation patterns and soil characteristics has been analysed in this work, showing a delay between them. Moreover, this technique has allowed the measurement of ground subsidence for a period (1993-1995) where no instrument information was available.

Performance of TerraSAR-X for urban subsidence monitoring: Murcia case study

This paper presents an analysis of the performance of TerraSAR-X for subsidence monitoring in urban areas. The city of Murcia has been selected as a test-site due to its high deformation rate and the set of extensometers deployed along the city that provide validation data. The obtained results have been compared with those obtained from ERS/ENVISAT data belonging to the same period and validated with the in-situ measurements.

Monitoring an earthfill dam using differential SAR interferometry: La Pedrera dam, Alicante, Spain

Surface displacement at the dykes of La Pedrera reservoir (SE Spain) has been measured by satellite differential Synthetic Aperture Radar (SAR) interferometry. At the main dyke, a displacement of about 13 cm along the satellite line of sight has been estimated between August 1995 and May 2010, from a dataset composed by ERS-1, ERS-2 and Envisat-ASAR images. Two independent short-term processing tasks were also carried out with ERS-2/Envisat-ASAR (from June 2008 to May 2010) and TerraSAR-X (from August 2008 to June 2010) images which have shown similar spatial and temporal displacement patterns. The joint analysis of historical instrument surveys and DInSAR-derived data has allowed the identification of a long-term deformation process which is reflected at the dam's surface and is also clearly recognizable in the inspection gallery. The plausible causes of the displacements measured by DInSAR are also discussed in the paper. Finally, DInSAR data have been used to compute the long-term settlement of La Pedrera dam, showing a good agreement with external studies. Consequently, this work demonstrates the integration of DInSAR with in-situ techniques which helps provide a complete spatial vision of the displacements in the dam thereby helping to differentiate the causal mechanisms.

A quasi-elastic aquifer deformational behavior: Madrid aquifer case study

The purpose of this paper is to analyze the quasi-elastic deformational behavior that has been induced by groundwater withdrawal of the Tertiary detrital aquifer of Madrid (Spain). The spatial and temporal evolution of ground surface displacement was estimated by processing two datasets of radar satellite images (SAR) using Persistent Scatterer Interferometry (PSI). The first SAR dataset was acquired between April 1992 and November 2000 by ERS-1 and ERS-2 satellites, and the second one by the ENVISAT satellite between August 2002 and September 2010. The spatial distribution of PSI measurements reveals that the magnitude of the displacement increases gradually towards the center of the well field area, where approximately 80 mm of maximum cumulated displacement is registered. The correlation analysis made between displacement and piezometric time series provides a correlation coefficient greater than 85% for all the wells. The elastic and inelastic components of measured displacements were separated, observing that the elastic component is, on average, more than 4 times the inelastic component for the studied period. Moreover, the hysteresis loops on the stress–strain plots indicate that the response is in the elastic range. These results demonstrate the quasi-elastic behavior of the aquifer. During the aquifer recovery phase ground surface uplift almost recovers from the subsidence experienced during the preceding extraction phase. Taking into account this unique aquifer system, a one dimensional elastic model was calibrated in the period 1997–2000. Subsequently, the model was used to predict the ground surface movements during the period 1992–2010. Modeled displacements were validated with PSI displacement measurements, exhibiting an error of 13% on average, related with the inelastic component of deformation occurring as a long-term trend in low permeability fine-grained units. This result further demonstrates the quasi-elastic deformational behavior of this unique aquifer system.

Twenty-year advanced DInSAR analysis of severe land subsidence: The Alto Guadalentín Basin (Spain) case study

A twenty-year period of severe land subsidence evolution in the Alto Guadalentín Basin (southeast Spain) is monitored using multi-sensor SAR images, processed by advanced differential interferometric synthetic aperture radar (DInSAR) techniques. The SAR images used in this study consist of four datasets acquired by ERS-1/2, ENVISAT, ALOS and COSMO-SkyMed satellites between 1992 and 2012. The integration of ground surface displacement maps retrieved for different time periods allows us to quantify up to 2.50 m of cumulated displacements that occurred between 1992 and 2012 in the Alto Guadalentín Basin. DInSAR results were locally compared with global positioning system (GPS) data available for two continuous stations located in the study area, demonstrating the high consistency of local vertical motion measurements between the two different surveying techniques. An average absolute error of 4.6 ± 4 mm for the ALOS data and of 4.8 ± 3.5 mm for the COSMO-SkyMed data confirmed the reliability of the analysis. The spatial analysis of DInSAR ground surface displacement reveals a direct correlation with the thickness of the compressible alluvial deposits. Detected ground subsidence in the past 20 years is most likely a consequence of a 100–200 m groundwater level drop that has persisted since the 1970s due to the overexploitation of the Alto Guadalentín aquifer system. The negative gradient of the pore pressure is responsible for the extremely slow consolidation of a very thick (> 100 m) layer of fine-grained silt and clay layers with low vertical hydraulic permeability (approximately 50 mm/h) wherein the maximum settlement has still not been reached.

Conhecimento e atitudes dos pais perante a criança com febre em contexto de serviço de urgência

Enquadramento – A febre na criança constitui uma das principais manifestações que impul-siona os pais na procura dos cuidados de saúde diferenciados, resultando na utilização ina-propriada de recursos. Objetivos – Identificar as variáveis sociodemográficas que interferem no conhecimento e nas atitudes dos pais perante a criança com febre; avaliar a influência do número de filhos no conhecimento e nas atitudes; identificar as fontes de informação que influenciam o conheci-mento e as atitudes dos pais. Material e Método – Estudo quantitativo, transversal, descritivo e correlacional. Recorreu-se ao questionário que inclui a caracterização sociodemográfica, contextual da criança, variá-veis clínicas de fontes de informação e questões que avaliam o conhecimento e as atitudes dos pais perante a febre na criança. A amostragem é não probabilística por conveniência (144 pais/cuidadores). Resultados – Amostra predominantemente feminina (86.8%), os homens são mais velhos (M=34.05 anos .6.45 anos); cerca de 9 em cada 10 das crianças eram acompanhadas pela mãe. Os sintomas que mais preocupam e levaram os participantes a recorrer ao Serviço de Urgência foram: vómitos/desidratação (66.4%), mau estado geral (64.6%), dificuldade respirató-ria (52.1%); em 58.5% dos casos de febre sem foco poder-se-ia ter utilizado os cuidados de saúde primários; a idade da criança e o sexo dummy revelaram-se preditoras dos conhecimen-tos e o sexo preditor das atitudes; as mulheres e os homens com mais idade e com filhos mais jovens possuem melhores conhecimentos; as mulheres têm atitudes mais adequadas. Conclusões – As mulheres possuem conhecimentos intermédios e revelam melhor atitude perante a febre. Quanto maior a escolaridade melhor é o conhecimento e os participantes que procuram como fonte de informação um profissional de saúde, possuem atitudes mais ade-quadas. Assume grande relevância a aquisição de competências que proporcionem aos pais/cuidadores ferramentas que os ajudem a lidar com a fobia da febre. Palavras-chave: Febre; Criança; Pais; Conhecimento; Atitudes; Serviço de Urgência.

Rural income distribution in Bolivia : a summary and evaluation of quantitative and qualitative information /

"Constitutes report no. 4 under contract no. 12-17-07-5-1651, June 24, 1976 (ERS-192-B-76)"