Wound-induced alterations in survival of60Co irradiated mice: importance of wound timing

Summary Wounding mice shortly before or shortly after lethal⁶⁰Co irradiation enhances survival. Survival of wounded-irradiated mice may be due to enhanced hematopoietic recovery as measured by endogenous spleen colony (E-CFU-s) formation.Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under research Work Unit 00129. Views presented in this paper are those of the authors; no endorsement by the Defense Nuclear Agency has been given or should be inferred.Research was conducted according to the principles enunciated in the Guide for the Care and Use of Laboratory Animals' prepared by the Institute of Laboratory Research, National Research Council.     

Platelet-derived growth factor stimulates synthesis of PtdIns(3,4,5)P3 by activating a PtdIns(4,5)P2 3-OH kinase.

Although the hormone-stimulated synthesis of 3-phosphorylated inositol lipids is known to form an intracellular signalling system, there is no consensus on the crucial receptor-regulated event in this pathway and it is still not clear which of the intermediates represent potential output signals. We show here that the key step in the synthesis of 3-phosphorylated inositol lipids in 3T3 cells stimulated by platelet-derived growth factor is the activation of a phosphatidylinositol(4,5)-bisphosphate (3)-hydroxy (PtdIns(4,5)P2 3-OH) kinase. A similar conclusion has been applied to explain the actions of formyl-Met-Leu-Phe on neutrophils, and it may be that receptors that couple through intrinsic tyrosine kinases or through G proteins stimulate the same step in 3-phosphorylated inositol lipid metabolism. The close parallel between these two mechanisms for the activation of PtdIns(4,5)P2 3-OH kinase and those described for the activation of another key signalling enzyme, phospholipase C (ref. 7), focuses attention on the product of the PtdIns(4,5)P2 3-OH kinase, PtdIns(3,4,5)P3, as a possible new second messenger.     

Light is a dominant mouse mutation resulting in premature cell death.

Light is a dominant mutant allele of the mouse brown locus which results in hairs pigmented only at their tips. The phenotype is due to premature melanocyte death. We have sequenced the tyrosinase-related protein-1 cDNA encoded at this locus from Light mice and found that it contains a single base alteration from wild-type, causing an Arg to Cys change in the protein. To further elucidate the mutant phenotype, we studied the expression of melanocyte specific genes in the skin of Light mice. We have demonstrated premature melanocyte death, but only in pigmented mice, indicating that the cell death is mediated through the inherent cytotoxicity of pigment production.     

The synthesis of stereoselectively labelled porphobilinogen and its incorporation into protoporphyrin-IX

Summary 11-(R)-²H porphobilinogen, stereospecifically labelled with deuterium in the aminomethylene group has been incorporated into protoporphyrin-IX by haemolysates of chicken erythrocytes. High field NMR spectroscopy confirms that the overall biochemical process is stereospecific, deuterium being retained at the -, -and -meso positions and lost from the -meso position.27 August 1986     

Rapid physiological adjustment of roots to localized soil enrichment

SOIL microsites rich in available nutrients are an important source of mineral nutrients for plants in many environments(1-5). Patchiness in nutrient availability below ground is analogous to resource availability in canopy gaps above ground(6). Although the physiological changes occurring in leaves exposed to sun and shade in canopy gaps are well known(7-9), we do not know any studies that show similar physiological changes in roots in enriched soil patches. Here we present evidence of large and rapid increases in the uptake kinetics of plant roots after creating nutrient-rich soil patches in the field. The mean rate of phosphate uptake at a given external phosphate concentration increased by as much as 80% for roots from enriched soil patches compared with roots of control patches treated with distilled water. The changes took place within days of patch treatment. This degree of plasticity was particularly notable for plants growing in soils of very low available phosphorus. These results showing rapid physiological plasticity of roots in fertile soil microsites have important implications for the theory and modelling of nutrient uptake in all soils.     

Forecasting using high‐frequency data: a comparison of asymmetric financial duration models

The first purpose of this paper is to assess the short‐run forecasting capabilities of two competing financial duration models. The forecast performance of the Autoregressive Conditional Multinomial–Autoregressive Conditional Duration (ACM‐ACD) model is better than the Asymmetric Autoregressive Conditional Duration (AACD) model. However, the ACM‐ACD model is more complex in terms of the computational setting and is more sensitive to starting values. The second purpose is to examine the effects of market microstructure on the forecasting performance of the two models. The results indicate that the forecast performance of the models generally decreases as the liquidity of the stock increases, with the exception of the most liquid stocks. Furthermore, a simple filter of the raw data improves the performance of both models. Finally, the results suggest that both models capture the characteristics of the micro data very well with a minimum sample length of 20 days. Copyright © 2008 John Wiley & Sons, Ltd.     

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 -     

Non-canonical activation of Notch signaling/target genes in vertebrates

Evolutionarily conserved Notch signaling orchestrates diverse physiological mechanisms during metazoan development and homeostasis. Classically, ligand-activated Notch receptors transduce the signaling cascade through the interaction of DNA-bound CBF1-co-repressor complex. However, recent reports have demonstrated execution of a CBF1-independent Notch pathway through signaling cross-talks in various cells/tissues. Here, we have tried to congregate the reports that describe the non-canonical/CBF1-independent Notch signaling and target gene activation in vertebrates with specific emphasis on their functional relevance.     

Newly identified loci that influence lipid concentrations and risk of coronary artery disease

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.