Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity

Expression of oncogenic Ras in primary human cells activates p53, thereby protecting cells from transformation. We show that in Ras-expressing IMR-90 cells, p53 is phosphorylated at Ser33 and Ser46 by the p38 mitogen-activated protein kinase (MAPK). Activity of p38 MAPK is regulated by the p53-inducible phosphatase PPM1D, creating a potential feedback loop. Expression of oncogenic Ras suppresses PPM1D mRNA induction, leaving p53 phosphorylated at Ser33 and Ser46 and in an active state. Retrovirus-mediated overexpression of PPM1D reduced p53 phosphorylation at these sites, abrogated Ras-induced apoptosis and partially rescued cells from cell-cycle arrest. Inactivation of p38 MAPK (the product of Mapk14) in vivo by gene targeting or by PPM1D overexpression expedited tumor formation after injection of mouse embryo fibroblasts (MEFs) expressing E1A+Ras into nude mice. The gene encoding PPM1D (PPM1D, at 17q22/q23) is amplified in human breast-tumor cell lines and in approximately 11% of primary breast tumors, most of which harbor wildtype p53. These findings suggest that inactivation of the p38 MAPK through PPM1D overexpression resulting from PPM1D amplification contributes to the development of human cancers by suppressing p53 activation.     

Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis

Familial expansile osteolysis (FEO, MIM 174810) is a rare, autosomal dominant bone disorder characterized by focal areas of increased bone remodelling. The osteolytic lesions, which develop usually in the long bones during early adulthood, show increased osteoblast and osteoclast activity. Our previous linkage studies mapped the gene responsible for FEO to an interval of less than 5 cM between D18S64 and D18S51 on chromosome 18q21.2-21.3 in a large Northern Irish family. The gene encoding receptor activator of nuclear factor-kappa B (RANK; ref. 5), TNFRSF11A, maps to this region. RANK is essential in osteoclast formation. We identified two heterozygous insertion mutations in exon 1 of TNFRSF11A in affected members of four families with FEO or familial Paget disease of bone (PDB). One was a duplication of 18 bases and the other a duplication of 27 bases, both of which affected the signal peptide region of the RANK molecule. Expression of recombinant forms of the mutant RANK proteins revealed perturbations in expression levels and lack of normal cleavage of the signal peptide. Both mutations caused an increase in RANK-mediated nuclear factor-kappaB (NF-kappaB) signalling in vitro, consistent with the presence of an activating mutation.     

Multidimensional Item Response Theory Models with Collateral Information as Poisson Regression Models

Multiple choice items on tests and Likert items on surveys are ubiquitous in educational, social and behavioral science research; however, methods for analyzing of such data can be problematic. Multidimensional item response theory models are proposed that yield structured Poisson regression models for the joint distribution of responses to items. The methodology presented here extends the approach described in Anderson, Verkuilen, and Peyton (2010) that used fully conditionally specified multinomial logistic regression models as item response functions. In this paper, covariates are added as predictors of the latent variables along with covariates as predictors of location parameters. Furthermore, the models presented here incorporate ordinal information of the response options thus allowing an empirical examination of assumptions regarding the ordering and the estimation of optimal scoring of the response options. To illustrate the methodology and flexibility of the models, data from a study on aggression in middle school (Espelage, Holt, and Henkel 2004) is analyzed. The models are fit to data using SAS.     

Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins

Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules.     

Differential responses to nitrogen form and concentration for Oryzopsis hymenoides and Elymus lanceolatus

In a greenhouse experiment, effects of nitrogen form and concentration on productivity and dry matter allocation differed between two species native to semiarid ecosystems of the Great Basin. Aboveground production of green surface area and of dry matter were consistently enhanced by increased nitrogen for the rhizomatous grass Elymus lanceolatus , but not for the bunchgrass Oryzopsis hymenoides . These differences were likely due to inherently low growth rates of O. hymenoides . Aboveground dry matter allocation also differed between the two species. O. hymenoides had more leaves per tiller with increased nitrogen, whereas leaf size but not number increased for E. lanceolatus . Furthermore, increases in tiller density with increased nitrogen for E. lanceolatus were almost three times greater than those for O. hymenoides . E. lanceolatus , but not O. hymenoides , was sensitive to the form of nitrogen supplied to the plants. When NH 4 -N was the only form of nitrogen supplied, high concentrations of NH 4 -N inhibited aboveground production of E. lanceolatus .     

Coordination of branch orientation and photosynthetic physiology in the Joshua tree ( Yucca brevifolia )

Despite the profusion of light in deserts, morphological adaptations to increase light interception are common among desert plants. We studied branch orientation and related physiological parameters in the Mojave Desert Joshua tree, Yucca brevifolia (Agavaceae). Azimuth and inclination were measured on all leaf rosettes of 44 Y. brevifolia trees. Interception of solar radiation was modeled for leaves in hypothetical rosettes facing due south and due north in December, March, and June. Carbon isotope discrimination, nitrogen content, and conductance of water vapor were measured in leaves from north- and south-facing rosettes. Rosette azimuths were nonrandom; rosettes predominantly faced southeast. North-facing rosettes were more steeply inclined than those facing south. The preponderance of south-facing rosettes reduces self-shading and increases interception of solar radiation during the winter-spring growth period. Stomatal conductance was higher for leaves in south-facing than in north-facing rosettes. Nevertheless, discrimination against 13 C was less in leaves of south-facing rosettes, indicating that average intercellular CO 2 concentration was also lower. South-facing whorls had higher leaf nitrogen content. Greater allocation of nitrogen to leaves in south-facing whorls probably results in those leaves having a greater photosynthetic capacity than their north-facing counterparts. Orientation of rosettes to increase interception of sunlight during the period most favorable for photosynthesis, coupled with allocation of nutrients to maintain a higher photosynthetic capacity in those rosettes, should significantly increase whole-plan carbon gain in Y. brevifolia .     

Depletion of soil moisture by two cold-desert bunchgrasses and effects on photoshythetic performance

This study compared the abilities of two cool-season bunchgrasses to extract moisture from a drying soil and compared photosynthetic and stomatal responses of the two species as soil moisture supplies were depleted. When grown in 49-L pots in a greenhouse, Leymus cinereus extracted more water from the soil and maintained higher gas exchange rates to lower absolute amounts of soil water than did Agropyron desertorum . The soil water content at the lower limit of extraction was 10.3% for L. cinereus and 13.3% for A. desertorum . When soil moisture was expressed as extractable soil water, there was little difference between the species in pattern of water use. Both species maintained high stomatal conductances (g w ) and photosynthetic rates (A) until extractable soil moisture was reduced to about 15%. For field-grown plants under severe water stress, A was higher in L. cinereus than in A. desertorum at comparable leaf water potentials. The relationship between A and g w was similar for the two species; higher A in L. cinereus was a consequence of higher g w . Thus, higher A in L. cinereus is achieved through some sacrifice of water-use efficiency.     

Roost sites used by Sandhill Crane staging along the Platte River, Nebraska

We assessed the influence of water depth, extent of unobstructed view, and human disturbance features on use of roost sites by Sandhill Cranes along the Platte River, Nebraska, during spring migratory stopover. Aerial photos taken near dawn were used to determine areas of flock use and habitat availability in four sample reaches, and measurements were made on the ground at flock roost areas. In general, depths of 1-13 cm were used by sandhill cranes in greater proportion than those available. Exposed sandbars and depths >20 cm were avoided, while depths of 14-19 cm were used in proportion to their availability. Sites 11-50 m from the nearest visual obstruction were used significantly greater than their availability, while sites 0-4 and >50 m from visual obstructions were avoided. Sandhill Cranes avoided sites near paved roads, gravel roads, single dwellings, and bridges when selecting roost sites; however, they did not appear to be disturbed by private roads, groups of residential buildings, gravel pits, railroads, or electrical transmission lines.     

The anatomy and taxonomy of Vanclevea (Asteraceae)

Wood, leaf, and floral anatomy of Vanclevea stylosa is compared with that of several possibly related species in the genera Acamptopappus, Eastwoodia, Grindelia, Haplopappus, and Petradoria. Although V. stylosa was originally described as a Grindelia, it is clearly distinct from that genus. Of the taxa studied, it is most closely allied to Haplopappus salincinus and H. scopulorum. The taxonomy, morphology, and distribution of the monotypic Vanclevea are detailed, and known exsiccatae are listed.