On a compris la toxicité du plomb / Jean-Luc Goudet - Futura-Sciences / http://www.futura-sciences.com/fr/sinformer/actualites/news/t/medecine/d/on-a-compris-la-toxicite-du-plomb_11841/

En se fixant sur certaines enzymes, le plomb empêche leur fonctionnement. La raison : sous sa forme ionique, l'atome de ce métal est bien plus volumineux que ce que l'on croyait. C'est la réponse à une vieille énigme mais aussi un espoir pour des thérapies futures contre le saturnisme.

Depuis des siècles, on sait que le plomb est un dangereux poison. Ingéré, il produit différents troubles (anémie et problèmes digestifs). A doses plus fortes, il attaque le système nerveux. C'est le saturnisme. Ces effets sont plus marqués chez l'enfant et le saturnisme infantile est dans de nombreux pays une maladie très grave directement liée aux conditions de pauvreté.

Comme remède, on ne connaît aujourd'hui que des produits chélateurs, c'est-à-dire des composés organiques fixant les métaux. Leur gros défaut est de ne pas faire de différence entre les bons et les mauvais. Ces chélateurs agrègent aussi le calcium ou le zinc qui, eux, sont utiles à l'organisme. Il serait donc utile de comprendre précisément l'action de ce métal sur le métabolisme.

Protubérance atomique

C'est dans les propriétés de l'atome lui-même que deux chercheurs du Laboratoire de chimie théorique (LCT) de l'université Paris VI ont trouvé les racines du mal. Olivier Parisel et Christophe Gourlaouen ont étudié l'action du plomb sur deux protéines, en l'occurrence la calmoduline, impliquée dans le transport du calcium, et une enzyme, la déshydratase de l'acide delta-aminolévulinique (ou Alad), qui participe à la fabrication de l'hémoglobine. On sait que l'activité des deux est dégradée par l'action du plomb, qui conduit donc à à la fois à un mauvais métabolisme du calcium et à une anémie.

Le métal provoque ses dégât quand il se fixe sur l'une de ces protéines. Les chercheurs ont découvert que sous sa forme ionisée Pb²⁺, l'atome de plomb augmente de volume. « Les deux électrons de la couche la plus externe de Pb²⁺ ne créent plus la densité sphérique observée habituellement autour de l'atome de plomb, mais un nuage électronique protubérant ! Ce qui empêche les substrats naturels de se fixer correctement sur les sites actifs des enzymes et ces dernières de fonctionner normalement » détaille Olivier Parisel. Ainsi, la calmoduline présente quatre sites de fixation de calcium. Le plomb vient s'accrocher à sa place. Même s'il n'occupe qu'un des quatre emplacements disponibles, son encombrement plus important empêche l'enzyme d'adopter la forme idéale pour son fonctionnement (les changements de configuration d'une enzyme sont l'une des clés de son action catalytique).

En poussant plus avant la compréhension des effets du plomb, les chercheurs espèrent bien que cette voie permettra à terme de mettre au point des produits à fonction antisaturnisme plus efficaces et avec moins d'effets secondaires que les actuels chélateurs.

Published online: 17 May 2007; | doi:10.1038/news070514-19 / http://www.nature.com/news/2007/070514/full/070514-19.html

Mosquito genome leaves researchers itching for more

As a second mosquito species is sequenced, news@nature.com looks back to see what these genomes do for science. / Heidi Ledford

What's new?

Aedes aegypti looks different and has a much different genome to its malaria-carrying cousin. James Gathany, CDC

Today scientists officially release the genome sequence of one of humanity's least beloved neighbours: the mosquito Aedes aegypti. A preliminary analysis of the sequence is published online in the journal Science, opening the floodgates on a variety of different research approaches aimed at controlling the insect and the diseases it carries.

Wait - this sounds awfully familiar. Didn't they already do this?

They sequenced the Anopheles gambiae genome four and a half years ago. That was a totally different mosquito.

Are they really so different?

The key distinction between the two is that a bite from a female A. gambiae can give you malaria, whereas a bite from A. aegypti could give you yellow fever or dengue. They also look very different.

The two mosquitoes diverged in evolution about 150 million years ago. "They are about as different as you can get in the mosquito world," says David Severson, a biologist at the University of Notre Dame in Indiana who participated in both sequencing projects. "They've had a long time to go off and do their own thing."

During that time, the A. aegypti genome swelled to 1.38 billion base pairs, five times the size of A. gambiae's genome (a third the size of the human genome). But the two mosquitoes have approximately the same number of genes.

What have researchers managed to do with the A. gambiae sequence so far?

Researchers have taken a variety of different strategies for using the A. gambiae genome sequence to further their attempts to control malaria. For example, molecular entomologist Flaminia Catteruccia of Imperial College London has been trawling through the A. gambiae genome in search of genes responsible for sex determination. Her ultimate goal is to flood wild mating populations with sexually active but genetically sterile male mosquitoes.

Meanwhile, Liangbiao Zheng of Yale University in New Haven, Connecticut, has been using the sequence to study the interactions between the mosquito and the malaria parasite. The hope is to use information about how the parasite evades the mosquito's immune defences to find ways to bolster A. gambiae's defences against malaria. Zheng and his colleagues have found several key genes that regulate the mosquito's response to infection. They are also comparing strains of A. gambiae that vary in their degree of resistance to the parasite, in the hope of finding the genetic regions responsible for increased or decreased immunity.

Has anyone worked out how to stop the mozzies from biting humans?

Some have focused their research on this, yes, with an eye to developing new insect repellents or to creating A. gambiae strains that can't hone in on their next human meal. Several studies have surveyed the genome for possible olfactory genes and have come up with a list of new targets.

Has any of this translated into practical applications?

It will be a long time before most of these findings can make the lab-to-field leap. "It isn't like 'We have the genome so now we can solve everything'," says Vishvanath Nene, a researcher at the J. Craig Venter Institute who worked on the A. aegypti genome. "But we are a step closer."

One technology that could make this leap soon is a method that uses gene expression patterns to determine whether a mosquito is resistant to insecticides. The traditional way of screening for insecticide resistance relied on testing individual mosquitoes against many, many individual herbicides. Using gene expression instead would speed up the process.

Are there other mosquito genomes out there too?

Early drafts of a genome sequence from Culex pipiens, the mosquito that carries elephantiasis and West Nile disease, are available.

And are there more to sequence?

Lots. There are about 3,500 species of mosquitoes, in three subfamilies - Anophelinae, Culicinae and Toxorhynchitinae. The three sequenced mozzies mentioned above fall into the first two subfamilies. Of them, only C. pipiens is common in North America or Europe.

There's actually more work to be done on A. gambiae too. The genome they sequenced turns out to have come from a lab strain that was actually a hybrid of two common subspecies. So now they have to sequence them individually to get the full picture.

What about other insects?

A motley crew of other unpleasant bloodsucking disease-carriers is already crowding the sequencing pipeline. At various stages in the sequencing process are: the deer tick, a scourge particularly in the United States because it can carry the bacterium that causes Lyme disease; the body louse, which can cause epidemic typhus; two different sand flies that can transmit leishmaniasis; and the tsetse fly, which can spread African sleeping sickness.

References

1. Nene V., et al. Science, doi:10.1126/science.1138878 (2007).
2. Holt R. A., et al. Science, 298 . 129 - 149 (2002).

Published online: 17 May 2007; | doi:10.1038/news070514-18 / http://www.nature.com/news/2007/070514/full/070514-18.html

Polar ocean is sucking up less carbon dioxide

Windy waters may mean less greenhouse gas is stored at sea. / Michael Hopkin

Colder waters can hold more dissolved gas. Getty

 

The ability of the Southern Ocean to remove carbon dioxide from the atmosphere is being eroded by climate change, say environmental researchers. If the trend [tendance] continues, then the ability of this 'carbon sink' to deal with humankind's greenhouse emissions will be impaired.

Roughly half of the carbon dioxide that enters the atmosphere is absorbed by the world's oceans, so as greenhouse emissions increase, the amount taken up by the oceans should increase in proportion. But the new research suggests that the Southern Ocean is not keeping pace with rising emissions. These Antarctic waters are an important sink for carbon dioxide, thanks to ocean currents and cold temperatures - they are thought to account for some 15% of the world's oceanic carbon-storage capacity.

Researchers led by Corinne Le Quéré of the Max Planck Institute of Biochemistry in Martinsried, Germany, took data from 11 coastal monitoring stations in Antarctica and on islands in the Southern Ocean to measure the amount of carbon dioxide being stored and released by the ocean. They then compared this measurements of global atmospheric carbon dioxide levels to work out the change in the performance of the carbon sink.

Since 1981, the percentage of atmospheric carbon dioxide that the Southern Ocean can hold has decreased, the researchers report in a study published online by Science. The trend suggests that, for each decade, the annual capacity of the ocean to store carbon has gone down by 0.08 gigatonnes compared with expectations. On average, the ocean stores between 0.1 and 0.6 gigatonnes a year.

This is a small amount compared with the roughly 8 gigatonnes of carbon dioxide pumped out each year by human activities such as energy generation. But any decline is important, as oceans are an important long-term sink. If humans can bring carbon dioxide emissions under control in the long term, the world's oceans are predicted to sequester between 70% and 80% of the total net anthropogenic emissions of the industrial era.

Winds of change

The main cause of the changes seems to be a relatively rapid increase in average wind strengths over the Southern Ocean, Le Quéré and her team report. These stronger winds, thought to be driven by the depletion of the ozone layer over Antarctic regions, churn up the ocean and bring more dissolved carbon up from the depths.

This was unexpected, says Le Quéré. But when the researchers plugged their data into a computer model and removed these stronger winds, they did indeed find that much of the observed reduction in the carbon sink disappeared.

An increase in global temperature is predicted to worsen the effect, since warmer waters hold less gas.

South to north

"The possibility that in a warmer world the Southern Ocean - the strongest ocean sink - is weakening, is a cause for concern," comments Chris Rapley, director of the British Antarctic Survey in Cambridge, UK.

The Southern Ocean is the only body of water for which this trend has been definitely spotted and quantified, says Le Quéré, although shorter-term studies suggest that a similar process may be occurring in the North Atlantic.

If the phenomenon is happening world-wide, this would undoubtedly affect efforts to stabilize atmospheric greenhouse gases.

A reduction in sink capacities will make it harder for international efforts, such as carbon trading and changes in methods of energy generation, to set achievable targets for stabilizing greenhouse-gas levels. But Le Quéré says that such efforts now need to be redoubled, rather than accepting that greenhouse gas levels will be higher in future. "Targets should depend on the level of danger [from global warming]," she says.

References : Le Quéré C., et al. Science, doi:10.1126/science.1136188 (2007).