Aromatase (Cyp19) expression is up-regulated by targeted disruption of Dax1

DAX-1 [dosage-sensitive sex reversal, adrenal hypoplasia congenita (AHC) critical region on the X chromosome, gene 1] is an orphan nuclear receptor that represses transcription by steroidogenic factor-1 (SF-1), a factor that regulates expression of multiple steroidogenic enzymes and other genes involved in reproduction. Mutations in the human DAX1 gene (also known as AHC) cause the X-linked syndrome AHC, a disorder that is associated with hypogonadotropic hypogonadism also. Characterization of Dax1-deficient male mice revealed primary testicular defects that included Leydig cell hyperplasia (LCH) and progressive degeneration of the germinal epithelium, leading to infertility. In this study, we investigated the effect of Dax1 disruption on the expression profile of various steroidogenic enzyme genes in Leydig cells isolated from Dax1-deficient male mice. Expression of the aromatase (Cyp19) gene, which encodes the enzyme that converts testosterone to estradiol, was increased significantly in the Leydig cells isolated from mutant mice, whereas the expression of other proteins (e.g., StAR and Cyp11a) was not altered. In in vitro transfection studies, DAX-1 repressed the SF-1-mediated transactivation of the Cyp19 promoter but did not inhibit the StAR or Cyp11a promoters. Elevated Cyp19 expression was accompanied by increased intratesticular levels of estradiol. Administration of tamoxifen, a selective estrogen-receptor modulator, restored fertility to the Dax1-deficient male mice and partially corrected LCH, suggesting that estrogen excess contributes to LCH and infertility. Based on these in vivo and in vitro analyses, aromatase seems to be a physiologic target of Dax-1 in Leydig cells, and increased Cyp19 expression may account, in part, for the infertility and LCH in Dax1-deficient mice.

Sustainable Development and its Discontents

Sustainable development (or sustainability) is a decision-making framework for maintaining and achieving human well-being, both in the present and into the future. The framework requires both consideration and achievement of environmental protection, social justice and economic development. In that framework, environmental protection must be integrated into decisions about social and economic development, and social justice and economic viability must be integrated into decisions about environmental quality. First endorsed by the world’s nations in 1992, this framework is intended to provide an effective response to the twin global challenges of growing environmental degradation and widespread extreme poverty. Sustainability provides a framework for humans to live in harmony with nature, rather than at nature’s expense. It may therefore be one of the most important ideas to come out of the 20th century. In the last two decades, the framework has become a touchstone in nearly every economic sector and at every level of government, unleashing an extraordinary range of creativity in all of those realms. Sustainable development is having a significant effect on the practice of law and on the way in which laws are written and implemented. Understanding the framework is increasingly important for law makers and lawyers. As sustainable development (or sustainability) has grown in prominence, its critics have become more numerous and more vocal. Three major lines of criticism are that the term is “too boring” to command public attention, “too vague” to provide guidance, and “too late” to address the world’s problems. Critics suggest goals such as abundance, environmental integrity, and resilience. Beginning with the international agreements that shaped the concept of sustainable development, this Article provides a functional and historical analysis of the meaning of sustainable development. It then analyzes and responds to each of these criticisms in turn. While the critics, understood constructively, suggest ways of strengthening this framework, they do not provide a compelling alternative. The challenge for lawyers, law makers, and others is to use and improve this framework to make better decisions.

The Hague, Netherlands, 1891 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Nieuwste plan van 's Gravenhage : met de verschillende hieuwe bouwplannen, John C. Bignell graveur. It was published by John C. Bignell in 1891. Scale 1:10,000. Covers The Hague, Netherlands. Map in Dutch. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'RD_New (Rijksdriehoekstelsel), GCS Amersfoort' coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads and stations, street-railroads, drainage, canals, built-up areas and selected buildings, ground cover, parks, cemeteries, and more. Includes also index and advertisements in margins.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

Experience in Competitive Youth Sport and Needs Satisfaction: The Singapore Story

The purpose of this study was to examine the relationship between sport experiences and psychological needs satisfaction of Singapore high school athletes who were involved in inter-school competition. A total of 1250 school athletes from 22 sports participated in the study. The athletes were between 13 and 18 years old and had an average of 3 years of experience in school sport (SD=.18). Cluster analysis was employed to identify homogenous groups based on the seven developmental experiences domains of the Youth Experience Survey (YES 2.0; Hansen & Larson, 2005). A one-way analysis of variance (ANOVA) was conducted to determine whether differences existed among the clusters in terms of psychological needs satisfaction (i.e., sense of autonomy, perceived competence and relatedness). The results of the cluster analysis showed that there were different subgroups of athletes with distinct developmental experiences, and they varied in the degree to which their psychological needs were satisfied. Generally, subgroups that had high levels of positive experiences and low levels of negative experiences in sport had better fulfillment of psychological needs. It is important to ensure that policies and programmes are formulated, delivered and monitored effectively to promote positive experiences for youth who are involved in competitive sports.

(Table 1) Stable oxygen isotopic ratios and yearly snow accumulation of firn and ice cores from Svalbard

We analyse ice cores from Vestfonna ice cap (Nordaustlandet, Svalbard). Oxygen isotopic measurements were made on three firn cores (6.0, 11.0 and 15.5 m deep) from the two highest summits of the glacier located on the SW-NE and NW-SE central ridges. Sub-annual d18O cycles were preserved and could be counted visually in the uppermost parts of the cores, but deeper layers were affected by post-depositional smoothing. A pronounced d18O minimum was found near the bottom of the three cores. We consider candidates for this d18O signal to be a valuable reference horizon since it is also seen elsewhere in Nordaustlandet. We attribute it to isotopically depleted snow precipitation, which NCEP/NCAR reanalysis shows was unusual for Vestfonna, and came from northerly air during the cold winter of 1994/95. Finding the 1994/95 time marker allows establishment of a precise depth/age scale for the three cores. The derived annual accumulation rates indirectly fill a geographical gap in mass balance measurements and thus provide information on spatial and temporal variability of precipitation over the glacier for the period spanned by the cores (1992-2009). Comparing records at the two locations also reveals that the snow net accumulation at the easternmost part of Vestfonna was only half of that in the western part over the last 17 years.

(Table 1) Sea surface temperature reconstruction for eastern equatorial Pacific surface sediment samples

Significant uncertainties persist in the reconstruction of past sea surface temperatures in the eastern equatorial Pacific, especially regarding the amplitude of the glacial cooling and the details of the post-glacial warming. Here we present the first regional calibration of alkenone unsaturation in surface sediments versus mean annual sea surface temperatures (maSST). Based on 81 new and 48 previously published data points, it is shown that open ocean samples conform to established global regressions of Uk'37 versus maSST and that there is no systematic bias from seasonality in the production or export of alkenones, or from surface ocean nutrient concentrations or salinity. The flattening of the regression at the highest maSSTs is found to be statistically insignificant. For the near-coastal Peru upwelling zone between 11-15°S and 76-79°W, however, we corroborate earlier observations that Uk'37 SST estimates significantly over-estimate maSSTs at many sites. We posit that this is caused either by uncertainties in the determination of maSSTs in this highly dynamic environment, or by biasing of the alkenone paleothermometer toward El Niño events as postulated by Rein et al. (2005).

The Congressional globe.

Edited by Blair and Rives, 23d-30th Congress; by John C. Rives, 31st-38th Congr., 1st sess.; by F. & J. Rives, 38th Cong., 2d sess.-39th Cong.; by F. & J. Rives & George A. Bailey, 40th-42d Cong.

Identification, quantification and structuring of two-lane rural highway safety problems and solutions. Volume I - technical report. Final report.

Federal Highway Administration, Washington, D.C.

HVOSM studies of cross-slope breaks on highway curves. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.

Vehicle shoulder encroachment and lateral placement study. Final report.

Mode of access: Internet.

Teton Dakota, ethnology and history /

Dakota chronology p. 87-93.

An age dependent, absorbing, semi-Markov model of post-entitlement work histories of the disabled beneficiaries /

"June 1980."

Potters, their arts and crafts.

Mode of access: Internet.

Clinical hematology : a practical guide to the examination of the blood with reference to diagnosis /

Includes bibliographical references and index.

Evaluation of retroreflective markings to increase rail car conspicuity -- safety of highway-railroad grade crossings.

Transportation Systems Center, Cambridge, Mass.