Aggregation of Expanded Huntingtin in the Brains of Patients With Huntington Disease

Huntingtin containing an expanded polyglutamine causes neuronal death and Huntington disease. Although expanded huntingtin is found in virtually every cell type, its toxicity is limited to neurons of certain areas of the brain, such as cortex and caudate/putamen. In affected areas of the brain, expanded huntingtin is not found in its intact monomeric form. It is found instead in the form of N-terminal fragments, oligomers and polymers, all of which accumulate in the cortex. Whereas the oligomer is mostly soluble, the polymers and the fragments associate with each other and with other proteins to form the insoluble inclusions characteristic of the disease. It is likely that the aggregates containing expanded huntingtin are toxic to neurons, but it remains to be determined whether the oligomer or the inclusion is the toxic species.Key Words: huntingtin, polyglutamine, aggregation, oligomer, polymer, N-terminal fragments, transglutaminase     

Specificity and genetic polymorphism in the Vfm quorum sensing system of plant pathogenic bacteria of the genus Dickeya

The Vfm quorum sensing (QS) system is preponderant for the virulence of different species of the bacterial genus Dickeya. The vfm gene cluster encodes 26 genes involved in the production, sensing or transduction of the QS signal. To date, the Vfm QS signal has escaped detection by analytical chemistry methods. However, we report here a strain-specific polymorphism in the biosynthesis genes vfmO and vfmP, which is predicted to be related to the production of different analogues of the QS signal. Consequently, the Vfm communication could be impossible between strains possessing different variants of the genes vfmO/P. We constructed three Vfm QS biosensor strains possessing different vfmO/P variants and compared these biosensors for their responses to samples prepared from 34 Dickeya strains possessing different vfmO/P variants. A pattern of specificity was demonstrated, providing evidence that the polymorphism in the genes vfmO/P determines the biosynthesis of different analogues of the QS signal. Unexpectedly, this vfmO/P-dependent pattern of specificity is linked to a polymorphism in the ABC transporter gene vfmG, suggesting an adaptation of the putative permease VfmG to specifically bind different analogues of the QS signal. Accordingly, we discuss the possible involvement of VfmG as co-sensor of the Vfm two-component regulatory system.     

Impact of demography on extinction/fixation events

In this article we consider diffusion processes modeling the dynamics of multiple allelic proportions (with fixed and varying population size). We are interested in the way alleles extinctions and fixations occur. We first prove that for the Wright–Fisher diffusion process with selection, alleles get extinct successively (and not simultaneously), until the fixation of one last allele. Then we introduce a very general model with selection, competition and Mendelian reproduction, derived from the rescaling of a discrete individual-based dynamics. This multi-dimensional diffusion process describes the dynamics of the population size as well as the proportion of each type in the population. We prove first that alleles extinctions occur successively and second that depending on population size dynamics near extinction, fixation can occur either before extinction almost surely, or not. The proofs of these different results rely on stochastic time changes, integrability of one-dimensional diffusion processes paths and multi-dimensional Girsanov’s tranform.

     

Heterogeneous inhibition of photosynthesis over the leaf surface of Rosa rubiginosa L. during water stress and abscisic acid treatment: induction of a metabolic component by limitation of CO2 diffusion

The contribution of changes in stomatal conductance and metabolism in determining heterogeneous photosynthesis inhibition during dehydration and abscisic acid (ABA) feeding was investigated using detached leaves of Rosa rubiginosa L. The steady-state and maximal rates of electron transport under a transient high CO₂ concentration were monitored using chlorophyll fluorescence imaging. The decrease in electron transport rate induced by dehydration and ABA treatment almost reverted to the control rate under transient high CO₂ availability. Therefore, inhibition of photosynthesis was mainly mediated through stomatal closure. However, since reversion was not complete, a metabolic inhibition was also identified as a decrease in the maximal electron transport rate driven by carboxylation. Under dehydration or ABA feeding, as under low ambient CO₂ treatment, in 21% or 0.4% O₂, the lower the steady-state electron transport was, the lower was the maximal electron transport rate during transient high CO₂ availability. We conclude that low CO₂ availability reduced the capacity of ribulose-1,5-bisphosphate carboxylase-oxygenase (Rubisco) to drive electron transport. The potential contribution of Rubisco deactivation mediated by stomatal closure is discussed. Received: 1 February 1999 / Accepted: 15 June 1999     

Polyamine derivatives as selective RNaseA mimics

Site-selective scission of ribonucleic acids (RNAs) has attracted considerable interest, since RNA is an intermediate in gene expression and the genetic material of many pathogenic viruses. Polyamine-imidazole conjugates for site-selective RNA scission, without free imidazole, were synthesized and tested on yeast phenylalanine transfer RNA. These molecules catalyze RNA hydrolysis non-randomly. Within the polyamine chain, the location of the imidazole residue, the numbers of nitrogen atoms and their relative distances have notable influence on cleavage selectivity. A norspermine derivative reduces the cleavage sites to a unique location, in the anticodon loop of the tRNA, in the absence of complementary sequence. Experimental results are consistent with a cooperative participation of an ammonium group of the polyamine moiety, in addition to it’s binding to the negatively charged ribose-phosphate backbone, as proton source, and the imidazole moiety as a base. There is correlation between the location of the magnesium binding sites and the RNA cleavage sites, suggesting that the protonated nitrogens of the polycationic chain compete with some of the magnesium ions for RNA binding. Therefore, the cleavage pattern is specific of the RNA structure. These compounds cleave at physiological pH, representing novel reactive groups for antisense oligonucleotide derivatives or to enhance ribozyme activity.