The "backdoor pathway" of androgen synthesis in human male sexual development.

Mammalian sex determination (male versus female) is largely controlled by genes, whereas sex differentiation (development of reproductive structures) is largely controlled by hormones. Work in the 20th century indicated that female external anatomy was a "default" pathway of development not requiring steroids, whereas male genital development required testicular testosterone plus dihydrotestosterone (DHT) made in genital skin according to a "classic" pathway. Recent work added the description of an alternative "backdoor" pathway of androgen synthesis discovered in marsupials. Unique "backdoor steroids" are found in human hyperandrogenic disorders, and genetic disruption of the pathway causes disordered male sexual development, suggesting it plays an essential role. O'Shaughnessy and colleagues now show that the principal human backdoor androgen is androsterone and provide strong evidence that it derives from placental progesterone that is metabolized to androsterone in nontesticular tissues. These studies are essential to understanding human sexual development and its disorders

The beta subunit of the signal recognition particle receptor is a transmembrane GTPase that anchors the alpha subunit, a peripheral membrane GTPase, to the endoplasmic reticulum membrane.

The signal recognition particle receptor (SR) is required for the cotranslational targeting of both secretory and membrane proteins to the endoplasmic reticulum (ER) membrane. During targeting, the SR interacts with the signal recognition particle (SRP) which is bound to the signal sequence of the nascent protein chain. This interaction catalyzes the GTP-dependent transfer of the nascent chain from SRP to the protein translocation apparatus in the ER membrane. The SR is a heterodimeric protein comprised of a 69-kD subunit (SR alpha) and a 30-kD subunit (SR beta) which are associated with the ER membrane in an unknown manner. SR alpha and the 54-kD subunits of SRP (SRP54) each contain related GTPase domains which are required for SR and SRP function. Molecular cloning and sequencing of a cDNA encoding SR beta revealed that SR beta is a transmembrane protein and, like SR alpha and SRP54, is a member of the GTPase superfamily. Although SR beta defines its own GTPase subfamily, it is distantly related to ARF and Sar1. Using UV cross-linking, we confirm that SR beta binds GTP specifically. Proteolytic digestion experiments show that SR alpha is required for the interaction of SRP with SR. SR alpha appears to be peripherally associated with the ER membrane, and we suggest that SR beta, as an integral membrane protein, mediates the membrane association of SR alpha. The discovery of its guanine nucleotide-binding domain, however, makes it likely that its role is more complex than that of a passive anchor for SR alpha. These findings suggest that a cascade of three directly interacting GTPases functions during protein targeting to the ER membrane

The isolation of the humen gamma globin genes

Imperial Users onl

The Effects of Different Footprint Sizes and Cloud Algorithms on the Top-Of-Atmosphere Radiative Flux Calculation from the Clouds and Earths Radiant Energy System (CERES) Instrument on Suomi National Polar-Orbiting Partnership (NPP)

Only one Clouds and Earths Radiant Energy System (CERES) instrument is onboard the Suomi National Polar-orbiting Partnership (NPP) and it has been placed in cross-track mode since launch; it is thus not possible to construct a set of angular distribution models (ADMs) specific for CERES on NPP. Edition 4 Aqua ADMs are used for flux inversions for NPP CERES measurements. However, the footprint size of NPP CERES is greater than that of Aqua CERES, as the altitude of the NPP orbit is higher than that of the Aqua orbit. Furthermore, cloud retrievals from the Visible Infrared Imaging Radiometer Suite (VIIRS) and the Moderate Resolution Imaging Spectroradiometer (MODIS), which are the imagers sharing the spacecraft with NPP CERES and Aqua CERES, are also different. To quantify the flux uncertainties due to the footprint size difference between Aqua CERES and NPP CERES, and due to both the footprint size difference and cloud property difference, a simulation is designed using the MODIS pixel-level data, which are convolved with the Aqua CERES and NPP CERES point spread functions (PSFs) into their respective footprints. The simulation is designed to isolate the effects of footprint size and cloud property differences on flux uncertainty from calibration and orbital differences between NPP CERES and Aqua CERES. The footprint size difference between Aqua CERES and NPP CERES introduces instantaneous flux uncertainties in monthly gridded NPP CERES measurements of less than 4.0 W/sq. m for SW (shortwave) and less than 1.0 W/sq. m for both daytime and nighttime LW (longwave). The global monthly mean instantaneous SW flux from simulated NPP CERES has a low bias of 0.4 W/sq. m when compared to simulated Aqua CERES, and the root-mean-square (RMS) error is 2.2 W/sq. m between them; the biases of daytime and night- time LW flux are close to zero with RMS errors of 0.8 and 0.2 W/sq. m. These uncertainties are within the uncertainties of CERES ADMs. When both footprint size and cloud property (cloud fraction and optical depth) differences are considered, the uncertainties of monthly gridded NPP CERES SW flux can be up to 20 W/sq. m in the Arctic regions where cloud optical depth retrievals from VIIRS differ significantly from MODIS. The global monthly mean instantaneous SW flux from simulated NPP CERES has a high bias of 1.1 W/sq. m and the RMS error increases to 5.2 W/sq. m. LW flux shows less sensitivity to cloud property differences than SW flux, with uncertainties of about 2 W/sq. m in the monthly gridded LW flux, and the RMS errors of global monthly mean daytime and nighttime fluxes increase only slightly. These results highlight the importance of consistent cloud retrieval algorithms to maintain the accuracy and stability of the CERES climate data record

Molds on vegetables in Indianapolis retail markets

Mold growth on market vegetables presents a problem to the store-keeper. Fungi detract from a display of produce and in turn reduce the sale of such produce; and reduction in sales results in loss of the produce. All produce is susceptible to mold growth, some more than others. Studies of molds in local markets have been made by Fisher and Lentz. Fisher confined his work to the disease of fruits found in the markets at Evanston, Illinois; and Lentz studied molds on both fruits and vegetables in the Indianapolis markets. Lents\u27 studies included molds found on produce from the Indianapolis Producers Market and other markets, or wholesale outlets where the produce was offered for sale only to retail markets. Final grading by the commission houses assures the retailer better produce and may also eliminate some of the molds

Never Land

Poem by Walter R. Mille