The HIV-1(Lai) RNA dimerization. Thermodynamic parameters associated with the transition from the kissing complex to the extended dimer.

Retroviruses contain dimeric RNA consisting of two identical copies of the genomic RNA. The interaction between these two RNA molecules occurs near their 5' ends. A region upstream from the splice donor comprising an auto-complementary sequence has been identified as being responsible for the initiation of the formation of dimeric HIV-1(Lai) RNA. This region (SL1), part of the PSI encapsidation domain, can adopt a stem-loop structure. It has already been shown that this stem-loop structure can initiate the formation of two distinct dimers differing in their thermostability: a loop-loop dimer or 'kissing complex' and an extended dimer. We report here a study using UV and 1D NMR spectroscopy of the dimerization of a short oligoribonucleotide (23 nucleotides) spanning nucleotides 248-270 of the HIV-1(Lai) SL1 sequence, in order to derive the thermodynamic parameters associated with the transition from the loop-loop complex to the extended dimer. The temperature dependence of the UV absorbency shows an hypochromicity for this transition with a small enthalpy change equal to - 29.4 +/- 5 kcal x mol-1, together with a concentration independent transition which implies a monomolecular reaction. On the other hand, our NMR results don't indicate a dissociation of the GCGCGC sequence engaged in the loop-loop interaction during the rearrangement of the loop-loop complex into the extended dimer. Our data suggest that the loop-loop interaction is maintained during the temperature dependent conformational change while the intramolecular base-pairing of the stems is disrupted and then reconstituted to form an intermolecular base-pairing leading to an extended dimer.     

Did Vaccination Slow the Spread of Bluetongue in France?

Vaccination is one of the most efficient ways to control the spread of infectious diseases. Simulations are now widely used to assess how vaccination can limit disease spread as well as mitigate morbidity or mortality in susceptible populations. However, field studies investigating how much vaccines decrease the velocity of epizootic wave-fronts during outbreaks are rare. This study aimed at investigating the effect of vaccination on the propagation of bluetongue, a vector-borne disease of ruminants. We used data from the 2008 bluetongue virus serotype 1 (BTV-1) epizootic of southwest France. As the virus was newly introduced in this area, natural immunity of livestock was absent. This allowed determination of the role of vaccination in changing the velocity of bluetongue spread while accounting for environmental factors that possibly influenced it. The average estimated velocity across the country despite restriction on animal movements was 5.4 km/day, which is very similar to the velocity of spread of the bluetongue virus serotype 8 epizootic in France also estimated in a context of restrictions on animal movements. Vaccination significantly reduced the propagation velocity of BTV-1. In comparison to municipalities with no vaccine coverage, the velocity of BTV-1 spread decreased by 1.7 km/day in municipalities with immunized animals. For the first time, the effect of vaccination has been quantified using data from a real epizootic whilst accounting for environmental factors known to modify the velocity of bluetongue spread. Our findings emphasize the importance of vaccination in limiting disease spread across natural landscape. Finally, environmental factors, specifically those related to vector abundance and activity, were found to be good predictors of the velocity of BTV-1 spread, indicating that these variables need to be adequately accounted for when evaluating the role of vaccination on bluetongue spread.     

Genetic control of grain yield and grain physical characteristics in a bread wheat population grown under a range of environmental conditions

Key message

Genetic analysis of the yield and physical quality of wheat revealed complex genetic control, including strong effects of photoperiod-sensitivity loci.

Abstract

Environmental conditions such as moisture deficit and high temperatures during the growing period affect the grain yield and grain characteristics of bread wheat (Triticum aestivum L.). The aim of this study was to map quantitative trait loci (QTL) for grain yield and grain quality traits using a Drysdale/Gladius bread wheat mapping population grown under a range of environmental conditions in Australia and Mexico. In general, yield and grain quality were reduced in environments exposed to drought and/or heat stress. Despite large effects of known photoperiod-sensitivity loci (Ppd-B1 and Ppd-D1) on crop development, grain yield and grain quality traits, it was possible to detect QTL elsewhere in the genome. Some of these QTL were detected consistently across environments. A locus on chromosome 6A (TaGW2) that is known to be associated with grain development was associated with grain width, thickness and roundness. The grain hardness (Ha) locus on chromosome 5D was associated with particle size index and flour extraction and a region on chromosome 3B was associated with grain width, thickness, thousand grain weight and yield. The genetic control of grain length appeared to be largely independent of the genetic control of the other grain dimensions. As expected, effects on grain yield were detected at loci that also affected yield components. Some QTL displayed QTL-by-environment interactions, with some having effects only in environments subject to water limitation and/or heat stress.     

Design, synthesis and antiproliferative activity of tripentones: a new series of antitubulin agents

Structure-activity relationship studies of a new series of tripentones (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC(50)=15 nM) was shown to be a potent inhibitor of tubulin polymerization.     

Making way for molecular biology: institutionalizing and managing reform of biological science in a UK university during the 1980s and 1990s

Historians agree that the second half of the twentieth century saw widespread changes in the structure of biological science in universities. This shift was, and continues to be, characterized by the de-differentiation of nineteenth and early twentieth century disciplines, with increasing emphasis on the methods and authority of molecular fields. Yet we currently lack appreciation of the dynamics that underpinned these changes, and of their tangible effects on the working practices of those involved. In this article we examine the wholesale reform of biological science at the University of Manchester, England, that occurred in two successive steps in 1986 and 1993. We examine how reform was enabled by economic and political factors, as staff seized upon national pressures; in so doing, we emphasize how this reform was shaped by a generational view of the biological sciences as a one field, unified by molecular techniques. We assess how the success of these reforms was tied to new management policies that rewarded research activity in molecular fields, and refigured teaching as a punishment for research inactivity. We close by showing how our analysis fits amongst, and can contribute to, 'big picture' debates in the history and sociology of knowledge.     

Synthesis,inhibition of NO production and antiproliferative activities of some indole derivatives

The synthesis and the biological evaluation of pyrano[3,2-e]indoles and their reaction intermediates are described. The compounds prepared were evaluated for their inhibition of NO production, antioxidant activity and also for their ability to inhibit in vitro the growth of four human tumor cell lines: large lung carcinoma (COR-L23), alveolar basal epithelial carcinoma (A549), amelanotic melanoma (C32) and melanoma (A375). The two reaction intermediates, 5a and 5b, showed the highest inhibition of NO production in murine monocytic macrophage (IC₅₀?=?1.1?μM and IC₅₀?=?2.3 μM respectively). Compound 5a was the most active against melanotic melanoma (IC₅₀?=?11.8?μM) while the other compounds exhibited weak cytotoxicity with IC₅₀ values >50?μM on all cell lines.     

Phosphate-guanosine interactions. A model for the involvement of guanine derivatives in autocatalytic reactions of ribonucleic acids

Proton magnetic resonance was used to study the interactions between nucleosides and phosphate monoanion in dimethyl sulfoxide. Ribose was able to form two mutually exclusive 1:1 complexes involving either OH3' and OH5' or OH3' and OH2' as hydrogen bond donor groups. Deoxyribose could form only one of these complexes. A specific interaction of phosphate with the base moiety of nucleosides was observed only with guanosine. A 1:1 complex was formed involving the N(1)H and NH2(2) of guanine. Association constants for both the base and sugar complexes were determined to be in the range 50-60 M-1 at 21 degrees C in dimethyl sulfoxide. This value is more than 1 order of magnitude higher than that measured for guanine-cytosine base pair formation under the same conditions. Water addition to dimethyl sulfoxide led to a decrease of all association constants but the guanine-phosphate "pair" remained more stable than the guanine-cytosine base pair.     

Interactions of the 26-39 fragment of the cro protein from lambda bacteriophage with nucleic acids

A tetradecapeptide with a sequence identical to residues 26-39 of the cro protein from bacteriophage lambda has been synthesized. This peptide has no secondary structure in an aqueous buffer but adopts an alpha-helical conformation in the presence of 20% hexafluoroisopropanol. The fluorescence of the single tyrosyl residue of the cro protein fragment is quenched upon binding to nucleic acids. Proton magnetic resonance has been used to investigate complex formation of the cro protein fragment with a self-complementary decadeoxynucleotide d(AATTGCAATT). Changes in resonance positions and linewidths have been observed for both partners in the 4 complexes which are obtained when either the single-stranded or double-stranded oligonucleotide is mixed with either the random coil or the alpha-helical peptide. These studies are presently extended to the specific complex formed by the cro protein fragment with the OR3 operator sequence.