The meta-hydroxylation step in the phenylpropanoid pathway: a new level of complexity in the pathway and its regulation

Together in silico and genetic mining approaches have recently designated the CYP98 family of plant cytochromes P450 as the family of enzymes that catalyzes the meta-hydroxylation step in the phenylpropanoid pathway. This meta-hydroxylation is not catalyzed on the free p-coumaric acid as anticipated, but on its conjugates with shikimic, quinic, or phenyllactic acids. While all CYP98s have in common phenol meta-hydroxylase activity, p-coumaroylshikimate remains their preferred substrate. High expression of CYP98s is detected in lignifying tissues in stems, roots, and siliques. The CYP98A3 gene disruption in Arabidopsis thaliana leads to a drastic inhibition of lignin synthesis, cell growth, and plant development. The meta-hydroxylation of phenolic precursors is thus essential for higher plant development. Isolation of coding sequences belonging to the CYP98 family from basil, wheat, and extensive functional analysis of the recombinant enzymes, together with CYP98s from other plant taxa, helps shedding some light on mechanisms of P450s evolution. Most importantly, the occurrence of the meta-hydroxylation on esters of shikimic or quinic acids introduces a new biochemical regulation mechanism in the phenylpropanoid pathway.     

Human reliability analysis: A critique and review for managers

In running our increasingly complex business systems, formal risk analyses and risk management techniques are becoming more important part to managers: all managers, not just those charged with risk management. It is also becoming apparent that human behaviour is often a root or significant contributing cause of system failure. This latter observation is not novel; for more than 30 years it has been recognised that the role of human operations in safety critical systems is so important that they should be explicitly modelled as part of the risk assessment of plant operations. This has led to the development of a range of methods under the general heading of human reliability analysis (HRA) to account for the effects of human error in risk and reliability analysis. The modelling approaches used in HRA, however, tend to be focussed on easily describable sequential, generally low-level tasks, which are not the main source of systemic errors. Moreover, they focus on errors rather than the effects of all forms of human behaviour. In this paper we review and discuss HRA methodologies, arguing that there is a need for considerable further research and development before they meet the needs of modern risk and reliability analyses and are able to provide managers with the guidance they need to manage complex systems safely. We provide some suggestions for how work in this area should develop. But above all we seek to make the management community fully aware of assumptions implicit in human reliability analysis and its limitations.     

Nouvelles informations relatives aux variations temporaires de l'activite nitrifiante d'un sol evaluee au laboratoire. incidences d'un apport de matieres organiques

Abstract

The results reported in this paper confirm the seasonal influence on soil nitrifying activity estimated in the laboratory. The variations of this activity depend on different factors: climatic conditions, soil nature, occurence of plants, characteristics of the organic matter added to the soil.

A fresh organic matter (straw, for example) leads to reduced nitrifying activity immediately after its incorporation; its depressive action disappears after a month under laboratory condi‐tions. A decomposed organic matter, as a manure, produces no effect.

This work also shows the seasonal variations of the mineral nitrogen immobilization after addition of a fresh organic matter.     

Organ targeted prenatal gene therapy—how far are we?

Prenatal gene therapy aims to deliver genes to cells and tissues early in prenatal life, allowing correction of a genetic defect, before long-term tissue damage has occurred. In contrast to postnatal gene therapy, prenatal application can target genes to a large population of dividing stem cells, and the smaller fetal size allows a higher vector-to-target cell ratio to be achieved. Early-gestation delivery may allow the development of immune tolerance to the transgenic protein which would facilitate postnatal repeat vector administration if needed. Targeting particular organs will depend on manipulating the vector to achieve selective tropism and on choosing the most appropriate gestational age and injection method for fetal delivery. Intra-amniotic injection reaches the skin, and other organs that are bathed in the fluid however since gene transfer to the lung and gut is usually poor more direct injection methods will be needed. Delivery to the liver and blood can be achieved by systemic delivery via the umbilical vein or peritoneal cavity. Gene transfer to the central nervous system in the fetus is difficult but newer vectors are available that transduce neuronal tissue even after systemic delivery. Copyright © 2011 John Wiley & Sons, Ltd.