Science Progress (2004), 87 (3)

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The determinants of lifespan in the

nematode Caenorhabditis elegans:

a short primer

MARK GEANACOPOULOS

ABSTRACT

Transparent, easily-maintained, amenable to genetic manipulation, and

living for only a few weeks, the nematode Caenorhabditis elegans is a

leading animal model for the study of the determinants of lifespan. The

original genetic screen for increased longevity identified a mutant, age-1,

with a defect in one component of a signal transduction pathway. This

pathway functioned as a genetic switch and governed the decision whether to

enter a specialized larval form, dauer, that enables the worm to withstand the

scarcity of food or other stressful conditions. These age-1 worms had an

increased tendency to become dauers, but if they did not adopt the dauer

developmental pathway, they lived longer than wild type worms. age-1 and

other longevity mutants with dauer phenotypes are vigorous, indicating that

they do not suffer from a significant energy deficit, and stress resistant.

Mutation of genes encoding mitochondrial components was found to be

another means of extending the lifespan of the worm, although the associated

phenotypes suggest a deficiency of available energy. While there are now

many documented genetic manipulations which can extend the worm's

lifespan, it has been difficult to come to definite conclusions as to the

mechanism(s) by which lifespan is extended. The most carefully studied

mutant strains have complex changes in gene expression and metabolism

making it difficult to ascertain what changes are critical.

The free radical theory of aging is the dominant biochemical theory of

aging, and the phenotypes of the well-characterized longevity mutants

worm can be accommodated to it. However discrete interventions to lower

reactive oxygen species, or mitigate their effects, have not produced

consistent easily-interpretable results in terms of lifespan extension.

It has become clear that the insulin-dependent signalling mechanism that

regulates lifespan in the worm functions in the context of a complex

endocrine system and the hormonal control of aging is an emerging focus

of research in worms and higher organisms.

Keywords: Caenorhabditis elegans, determinants of lifespan

Mark Geanacopoulos is based at the National Institute of Diabetes and Digestive and Kidney

Diseases, National Institutes of Health, 2 Democracy Plaza, Rm 642B, 6707 Democracy

Boulevard, MSC 5458, Bethesda,MD 20892-5458, USA.

E-mail: GeanacoM@intra.niddk.nih.gov

Helicobacter pylori: current status

and future prospects

RACHEL O'MAHONY1, DINO VAIRA2, JOHN HOLTON1 AND

CHRISTELLE BASSET3

ABSTRACT

Helicobacter pylori is a global pathogen that causes severe gastrointestinal

diseases leading to a significant morbidity and mortality. There is an

effective treatment for peptic ulcer disease, however, this is being compromised

by an increase in the prevalence of antibiotic resistance. Although

alternative rescue regimens have been advocated, the best strategy would be

to prevent disease, especially in the case of gastric cancer for which there is

still no treatment. One approach is to inhibit the first step in the pathogenic

process ± adhesion of the organism to the host tissue. Another and probably

a better approach is vaccination, but clinical trials have so far been

unsuccessful. There is still a large uncertainty in relation to how H. pylori

causes disease. Knowledge from genomics, proteomics, and the relationship

between polymorphism of the bacterium and the host, as well as the

continuing investigation of the role played by important virulence factors

in the outcome of the disease, will help both in understanding pathogenesis of

disease and in the design of the best vaccine.

Keywords: Helicobacter, peptic ulcer, gastric cancer, management,

adhesion, genome, proteome, VacA, CagA

1Centre for Infectious Diseases & International Health, RF&UCL Medical School, UK.

2Department of Internal Medicine and Gastroenterology, University of Bologna, Italy.

3INSERM0114, Physiopathologie des Maladies Inflammatoires Intestinales, CHU Lille,

France.

Correspondence should be addressed to Dr John Holton, Centre for Infectious Diseases &

International Health, Royal Free and University College LondonMedical School, The

Windeyer Building, 46 Cleveland Street, London, W1T 4JF, UK.

E-mail: john.holton@uclh.org

Utilizing the charging effect in

scanning electron microscopy

HAI-BO ZHANG, REN-JIAN FENG AND KATSUMI URA

ABSTRACT

The charging effect of an insulating specimen from electron beam (e-beam)

irradiation may be utilized to facilitate imaging in the scanning electron

microscope (SEM). This has been confirmed by a great deal of experimental

work during the last three decades. Particularly, recent investigations

indicate that even located underneath insulating thin films that a low

energy e-beam cannot penetrate, conductors not biased and overlay marks,

are observable through a novel imaging pattern, charging contrast. Unlike

conventional SEM contrasts, which usually reflect surface characteristics,

the dynamic charging contrast can reveal information of underlying structures

without any external exciting signal. The authors consider that this

kind of charging contrast arises from the different redistribution rates of

secondary electrons returning to the surface under the surface local field of

the charged specimen. The charging contrast has the prospect of extending

the SEM application and forming new testing methods matched with the fast

development of integrated circuits.

Keywords: Scanning electron microscope (SEM), image contrast, insulator,

charging effect, surface local ®eld, secondary electron, redistribution,

integrated circuit measurement