Regulatory networks define phenotypic classes of human stem cell lines

Stem cells are defined as self-renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal and adult sources have been called stem cells, even though they range from pluripotent cells-typified by embryonic stem cells, which are capable of virtually unlimited proliferation and differentiation-to adult stem cell lines, which can generate a far more limited repertoire of differentiated cell types. The rapid increase in reports of new sources of stem cells and their anticipated value to regenerative medicine has highlighted the need for a general, reproducible method for classification of these cells. We report here the creation and analysis of a database of global gene expression profiles (which we call the 'stem cell matrix') that enables the classification of cultured human stem cells in the context of a wide variety of pluripotent, multipotent and differentiated cell types. Using an unsupervised clustering method to categorize a collection of approximately 150 cell samples, we discovered that pluripotent stem cell lines group together, whereas other cell types, including brain-derived neural stem cell lines, are very diverse. Using further bioinformatic analysis we uncovered a protein-protein network (PluriNet) that is shared by the pluripotent cells (embryonic stem cells, embryonal carcinomas and induced pluripotent cells). Analysis of published data showed that the PluriNet seems to be a common characteristic of pluripotent cells, including mouse embryonic stem and induced pluripotent cells and human oocytes. Our results offer a new strategy for classifying stem cells and support the idea that pluripotency and self-renewal are under tight control by specific molecular networks.     

The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease

The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.     

BOOK REVIEWS: Partnership and Participation by Ann Taket and Leroy White. Sustainable Development: Economics and Policy by P. K. Rao.

Systemic Practice and Action Research -     

Reduction and Understanding

Reductionism, in the sense of the doctrine that theories on different levels of reality should exhibit strict and general relations of deducibility, faces well-known difficulties. Nevertheless, the idea that deeper layers of reality are responsible for what happens at higher levels is well-entrenched in scientific practice. We argue that the intuition behind this idea is adequately captured by the notion of supervenience: the physical state of the fundamental physical layers fixes the states of the higher levels. Supervenience is weaker than traditional reductionism, but it is not a metaphysical doctrine: one can empirically support the existence of a supervenience relation by exhibiting concrete relations between the levels. Much actual scientific research is directed towards finding such inter-level relations. It seems to be quite generally held that the importance of such relations between different levels is that they are explanatory and give understanding: deeper levels provide deeper understanding, and this justifies the search for ever deeper levels. We shall argue, however, that although achieving understanding is an important aim of science, its correct analysis is not in terms of relations between higher and lower levels. Connections with deeper layers of reality do not generally provide for deeper understanding. Accordingly, the motivation for seeking deeper levels of reality does not come from the desire to find deeper understanding of phenomena, but should be seen as a consequence of the goal to formulate ever better, in the sense of more accurate and more-encompassing, empirical theories. This revised version was published online in July 2006 with corrections to the Cover Date.     

Managing livestock grazing for mule deer ( Odocoileus hemionus ) on winter range in the Great Basin

History and technical literature describing potential effects of livestock grazing on mule deer ( Odocoileus hemionus ) populations and winter range habitat are reviewed. Recommendations for livestock grazing on winter ranges within the Great Basin are advanced.     

Changes in Mule Deer Size in Utah

Trends in age-specific, eviscerated carcass weights were determined for hunter-harvested yearling and two-year-old buck mule deer. Carcass weights declined over an 11-year period from two areas of similar management, but with independenly collected data sets. Carcass weights also declined between the opening and second weekends of the hunt. Management implications are discussed.     

Consumption of fresh alfalfa hay by mule deer and elk

Tame mule deer and elk were fed fresh alfalfa hay at night and given various alternate forages during the day. This schedule, simulating farmland depredation feeding, yielded consumption values for field-growing alfalfa hay.