Deletion of the Nuclear Localization Sequences and C-Terminus of PTHrP Impairs Embryonic Mammary Development but also Inhibits PTHrP Production

Parathyroid hormone-related protein (PTHrP) can be secreted from cells and interact with its receptor, the Type 1 PTH/PTHrP Receptor (PTHR1) in an autocrine, paracrine or endocrine fashion. PTHrP can also remain inside cells and be transported into the nucleus, where its functions are unclear, although recent experiments suggest that it may broadly regulate cell survival and senescence. Disruption of either the PTHrP or PTHR1 gene results in many abnormalities including a failure of embryonic mammary gland development in mice and in humans. In order to examine the potential functions of nuclear PTHrP in the breast, we examined mammary gland development in PTHrP (1–84) knock-in mice, which express a mutant form of PTHrP that lacks the C-terminus and nuclear localization signals and which can be secreted but cannot enter the nucleus. Interestingly, we found that PTHrP (1–84) knock-in mice had defects in mammary mesenchyme differentiation and mammary duct outgrowth that were nearly identical to those previously described in PTHrP^−/− and PTHR1^−/− mice. However, the mammary buds in PTHrP (1–84) knock-in mice had severe reductions in mutant PTHrP mRNA levels, suggesting that the developmental defects were due to insufficient production of PTHrP by mammary epithelial cells and not loss of PTHrP nuclear function. Examination of the effects of nuclear PTHrP in the mammary gland in vivo will require the development of alternative animal models.     

Operation of a Benchtop Bioreactor

Fermentation systems are used to provide an optimal growth environment for many different types of cell cultures. The ability afforded by fermentors to carefully control temperature, pH, and dissolved oxygen concentrations in particular makes them essential to efficient large scale growth and expression of fermentation products. This video will briefly describe the advantages of the fermentor over the shake flask. It will also identify key components of a typical benchtop fermentation system and give basic instruction on setup of the vessel and calibration of its probes. The viewer will be familiarized with the sterilization process and shown how to inoculate the growth medium in the vessel with culture. Basic concepts of operation, sampling, and harvesting will also be demonstrated. Simple data analysis and system cleanup will also be discussed.     

Detection of Aldehydes and Their Conjugated Hydroperox Ydiene Precursors in Thermally-Stressed Culinary Oils and Fats: Investigations Using High Resolution Proton Nmr Spectroscopy

High field (400 and 600 MHz) proton NMR spectroscopy has been employed to investigate the thermally-induced autoxidation of glycerol-bound polyunsaturated fatty acids present in intact culinary frying oils and fats. Heating of these materials at 180°C for periods of 30, 60 and 90 min. generated a variety of peroxidation products, notably aldehydes (alkanals, trans-2-alkenals and alka-2, 4-dienals) and their conjugated hydroperoxydiene precursors. Since such aldehydes appear to be absorbed into the systemic circulation from the gut in vivo, the toxicological significance of their production during standard frying practices is discussed.     

Co-segregation of a gene encoding a deletion ligand for Tcrb-V3+ T cells with Mtv-3

A gene encoding the endogenous superantigen Mls^c, which deletes Tcrb-V3⁺ T cells in the NOD inbred mouse strain, was found to co-segregate with Mtv-3 on chromosome 11. This identifies a fourth gene encoding a deletion ligand for Tcrb-V3⁺ T cells and extends recently published observations in support of the hypothesis that a number of endogenous superantigens are the products of Mtv proviruses. Address correspondence and offprint requests to : K. Tomonari.     

A Bayesian Developmental Approach to Robotic Goal-Based Imitation Learning

A fundamental challenge in robotics today is building robots that can learn new skills by observing humans and imitating human actions. We propose a new Bayesian approach to robotic learning by imitation inspired by the developmental hypothesis that children use self-experience to bootstrap the process of intention recognition and goal-based imitation. Our approach allows an autonomous agent to: (i) learn probabilistic models of actions through self-discovery and experience, (ii) utilize these learned models for inferring the goals of human actions, and (iii) perform goal-based imitation for robotic learning and human-robot collaboration. Such an approach allows a robot to leverage its increasing repertoire of learned behaviors to interpret increasingly complex human actions and use the inferred goals for imitation, even when the robot has very different actuators from humans. We demonstrate our approach using two different scenarios: (i) a simulated robot that learns human-like gaze following behavior, and (ii) a robot that learns to imitate human actions in a tabletop organization task. In both cases, the agent learns a probabilistic model of its own actions, and uses this model for goal inference and goal-based imitation. We also show that the robotic agent can use its probabilistic model to seek human assistance when it recognizes that its inferred actions are too uncertain, risky, or impossible to perform, thereby opening the door to human-robot collaboration.     

Pre-exposure affects the olfactory response of Drosophila melanogaster to menthol

A modification of the trap assay (Woodard et al., 1989) was used to evaluate the response of Drosophila melanogaster (Meigen) to food media containing menthol. Dose-response curves for flies to mentholic foods were produced for flies that had been pre-exposed to menthol, during development and adult life, and flies that had not been exposed to menthol before the assay. Mentholic food media were less attractive to Drosophila than plain food medium. Rearing flies on a medium containing menthol reduced their aversion to some concentrations of menthol. The rearing effect was not simply due to lowered general activity levels resulting from developing in a medium containing menthol. There was a threshold concentration of menthol in the rearing medium below which we found no induced behavioural change.