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

Content Area Reading: A Modular Approach

The project is unique in two major respects. First, it greatly simplifies the participation of individual teachers by making available instructional modules prepared in advance for each textbook unit. Second, it coordinates the use of these modules with a diagnostic/prescriptive management system operated in the language arts program

Existence and Stability of Standing Pulses in Neural Networks : I Existence

We consider the existence of standing pulse solutions of a neural network integro-differential equation. These pulses are bistable with the zero state and may be an analogue for short term memory in the brain. The network consists of a single-layer of neurons synaptically connected by lateral inhibition. Our work extends the classic Amari result by considering a non-saturating gain function. We consider a specific connectivity function where the existence conditions for single-pulses can be reduced to the solution of an algebraic system. In addition to the two localized pulse solutions found by Amari, we find that three or more pulses can coexist. We also show the existence of nonconvex ``dimpled'' pulses and double pulses. We map out the pulse shapes and maximum firing rates for different connection weights and gain functions.Comment: 31 pages, 29 figures, submitted to SIAM Journal on Applied Dynamical System

Consumer attitudes towards sustainability attributes on food labels

Concerns about climate change and the general status of the environment have increased expectation that food products have sustainability credentials, and that these can be verified. There are significant and increasing pressures in key export markets for information on Greenhouse gas (GHG) intensity of products throughout its life-cycle. How this information is conveyed to consumers is a key issue. Labelling is a common method of communicating certain product attributes to consumers that may influence their choices. In a choice experiment concerning fruit purchase decisions, this study estimates willingness to pay for sustainability attributes by consumers in Japan and the UK. The role of label presentation format is investigated: text only, text and graphical, and graphical only. Results indicate that sustainability attributes influence consumers’ fruit purchase decisions. Reduction of carbon in fruit production is shown to be the least valued out of sustainability attributes considered. Differences are evident between presentation formats and between countries, with increased nutrient content being the most sensitive to format and country while carbon reduction is the most insensitive and almost always valued the least

Labelling sustainability - what consumers want, know and understand

With today’s concerns about the general status of the environment, there is an increasing expectation for products to have sustainability attributes. Labelling is a common method of letting consumers know more about what they have bought. Different consumers react differently towards various attributes on food labels and this may have an effect on their choices. It is helpful to understand which of the many attributes appeal to consumers and how much they may be willing to pay