RACK1 depletion in a mouse model causes lethality, pigmentation deficits and reduction in protein synthesis efficiency

The receptor for activated C-kinase 1 (RACK1) is a conserved structural protein of 40S ribosomes. Strikingly, deletion of RACK1 in yeast homolog Asc1 is not lethal. Mammalian RACK1 also interacts with many nonribosomal proteins, hinting at several extraribosomal functions. A knockout mouse for RACK1 has not previously been described. We produced the first RACK1 mutant mouse, in which both alleles of RACK1 gene are defective in RACK1 expression (ΔF/ΔF), in a pure C57 Black/6 background. In a sample of 287 pups, we observed no ΔF/ΔF mice (72 expected). Dissection and genotyping of embryos at various stages showed that lethality occurs at gastrulation. Heterozygotes (ΔF/+) have skin pigmentation defects with a white belly spot and hypopigmented tail and paws. ΔF/+ have a transient growth deficit (shown by measuring pup size at P11). The pigmentation deficit is partly reverted by p53 deletion, whereas the lethality is not. ΔF/+ livers have mild accumulation of inactive 80S ribosomal subunits by polysomal profile analysis. In ΔF/+ fibroblasts, protein synthesis response to extracellular and pharmacological stimuli is reduced. These results highlight the role of RACK1 as a ribosomal protein converging signaling to the translational apparatus.     

A habitat suitability model for pygmy rabbits ( Brachylagus iIdahoensis ) in southeastern Idaho

A habitat suitability model was developed for pygmy rabbit ( Brachylagus idahoensis ) habitat on the Idaho National Engineering and Environmental Laboratory (INEEL) in southeastern Idaho. Suitable pygmy rabbit areas were characterized by greater cover and density of total shrubs and big sagebrush ( Artemisia tridentata ), as well as greater forb cover. Soil texture also played an important role in distinguishing suitable pygmy rabbit areas from nonuse sites. Principal components analysis (PCA) of several vegetation variables and soil texture was used to develop a habitat suitability model for pygmy rabbit habitat. This model, which can be used to successfully distinguish between pygmy rabbit use and nonuse areas on the INEEL, has the potential for use throughout the pygmy rabbits range.     

Habitat use patterns within the home range of pygmy rabbits ( Brachylagus idahoensis ) in southeastern Idaho

Pygmy rabbits ( Brachylagus idahoensis ) are a small sagebrush ( Artemisia tridentata ) obligate lagomorph found within the Great Basin of northwestern United States. Because of its reliance on sagebrush, this species is thought to be experiencing a major range reduction as a result of loss of sagebrush habitat. To aid in conservation of this species, we need to better understand its use of the sagebrush environment. We estimated summer home range use patterns by relocating 5 radio-collared pygmy rabbits (3 females and 2 males) over a 24-hour cycle. We then compared soil texture, shrub density, height, and canopy cover between areas close to burrow entrances and areas of high use and low use. Mean home range sizes of female and male rabbits were 37.2 and 67.9 ha, respectively. Rabbits had disproportionate amounts of time (68.4% ± 9.1, s￣x ) and travel (63.0% ± 5.7, s￣x ) in areas within a 60-m radius of their burrows. Soil texture did not differ among the 3 areas, but shrub density, specifically big sagebrush, and forb density were significantly higher close to the burrow than in the high- and low-use areas. We conclude that pygmy rabbits are possibly burrow obligates and that their abundance and distribution are likely limited by available burrow sites.     

Vulnerability of Fremont cottonwood ( Populus fremontii Wats.) individuals to xylem cavitation

Embolism, the blockage of water transport in the xylem by air, is an important consequence of low water availability for all plant species. Riparian plants, since they typically experience mesic conditions, are not water stress tolerant and hence are vulnerable to xylem cavitation, the formation of emboli. We have constructed a composite vulnerability curve for Populus fremontii (Fremont cottonwood); assessed native state embolism, critical xylem pressure potential (Ψ cav ), and safety margin; and determined predawn and midday leaf water potential (Ψ L ) within a central New Mexico cottonwood population. Our results indicate (1) that this population of P. fremontii is extremely vulnerable to cavitation, with complete xylem blockage occurring at -2.25 MPa, and (2) that native state embolism is between 19% and 42%. Ψ cav was determined to be -1.36 MPa. Measurements of predawn Ψ L were typically near -0.5 MPa while midday Ψ L values averaged -1.7 MPa. Estimates of midday xylem pressure potential (Ψ px ) were -1.1 MPa. These values suggest that these individuals maintain small safety margins (0.26 MPa) between Ψ px and Ψ cav . This small safety margin may be detrimental under increased variation in water availability caused by anthropogenic alteration of river systems.     

Downregulation of NF-κB signaling by mutant huntingtin proteins induces oxidative stress and cell death

Accumulation of abnormal proteins and endoplasmic reticulum stress accompany neurodegenerative diseases including Huntington’s disease. We show that the expression of mutant huntingtin proteins with extended polyglutamine repeats differentially affected endoplasmic reticulum signaling cascades linked to the inositol-requiring enzyme-1 (IRE1) pathway. Thus, the p38 and c-Jun N-terminal kinase pathways were activated, while the levels of the nuclear factor-κB-p65 (NF-κB-p65) protein decreased. Downregulation of NF-κB signaling was linked to decreased antioxidant levels, increased oxidative stress, and enhanced cell death. Concomitantly, calpain was activated, and treatment with calpain inhibitors restored NF-κB-p65 levels and increased cell viability. The calpain regulator, calpastatin, was low in cells expressing mutant huntingtin, and overexpression of calpastatin counteracted the deleterious effects caused by N-terminal mutant huntingtin proteins. These results show that calpastatin and an altered NF-κB-p65 signaling are crucial factors involved in oxidative stress and cell death mediated by mutant huntingtin proteins.     

Unemployment variation over the business cycles: a comparison of forecasting models

Asymmetry has been well documented in the business cycle literature. The asymmetric business cycle suggests that major macroeconomic series, such as a country's unemployment rate, are non‐linear and, therefore, the use of linear models to explain their behaviour and forecast their future values may not be appropriate. Many researchers have focused on providing evidence for the non‐linearity in the unemployment series. Only recently have there been some developments in applying non‐linear models to estimate and forecast unemployment rates. A major concern of non‐linear modelling is the model specification problem; it is very hard to test all possible non‐linear specifications, and to select the most appropriate specification for a particular model. Artificial neural network (ANN) models provide a solution to the difficulty of forecasting unemployment over the asymmetric business cycle. ANN models are non‐linear, do not rely upon the classical regression assumptions, are capable of learning the structure of all kinds of patterns in a data set with a specified degree of accuracy, and can then use this structure to forecast future values of the data. In this paper, we apply two ANN models, a back‐propagation model and a generalized regression neural network model to estimate and forecast post‐war aggregate unemployment rates in the USA, Canada, UK, France and Japan. We compare the out‐of‐sample forecast results obtained by the ANN models with those obtained by several linear and non‐linear times series models currently used in the literature. It is shown that the artificial neural network models are able to forecast the unemployment series as well as, and in some cases better than, the other univariate econometrics time series models in our test. Copyright © 2004 John Wiley & Sons, Ltd.     

Introduction

The question of the existence of intelligent life on other worlds has never been a purely scientific one. Philosophical, religious and literary issues have been intertwined with scientific ones throughout the history of the “plurality of worlds” debate. This collection of papers in –Studies in History and Philosophy of Science– explores the interrelation of science, philosophy, religion and literature in debates about extraterrestrial life.     

Forecasting market impact costs and identifying expensive trades

Often, a relatively small group of trades causes the major part of the trading costs on an investment portfolio. Consequently, reducing the trading costs of comparatively few expensive trades would already result in substantial savings on total trading costs. Since trading costs depend to some extent on steering variables, investors can try to lower trading costs by carefully controlling these factors. As a first step in this direction, this paper focuses on the identification of expensive trades before actual trading takes place. However, forecasting market impact costs appears notoriously difficult and traditional methods fail. Therefore, we propose two alternative methods to form expectations about future trading costs. Applied to the equity trades of the world's second largest pension fund, both methods succeed in filtering out a considerable number of trades with high trading costs and substantially outperform no‐skill prediction methods. Copyright © 2008 John Wiley & Sons, Ltd.