Robert Sullivan and Franck Boué of the Central Hospital at Laval University in Quebec City have discovered that more than half of a sample of infertile Canadian men produce sperm carrying abnormally low quantities of the protein P34H. This finding, reported in the latest issue of Biology of Reproduction (vol 54, p 1018), may pave the way to new infertility treatments, and possibly new forms of contraception.

Infertility affects around 8 per cent of couples. In women, the problem is often a hormonal imbalance that can be quickly identified and remedied. But in men only a tiny proportion of cases are due to hormonal problems.

Some men’s fertility problems can be tied to obvious deficiencies such as low sperm counts or sperm that cannot swim normally. But unexplained male infertility is common—it is thought to underlie a large fraction of the 20 per cent of infertile couples for whom no explanation can be found for either partner.

Sullivan and Boué were interested in the role of proteins coating the sperm’s surface which bind to the zona pellucida, a transparent layer of sugar-bearing proteins that surrounds the egg. This binding is an essential first step in fertilisation.

The protein P34H, which the Canadian researchers identified on sperm in 1994, appears to be required for binding. It is added to the surface of sperm as they travel through the epididymis, a long tube in which sperm are stored before ejaculation.

The researchers compared the levels of P34H on sperm from fertile and infertile men, all of whom had normal sperm counts and sperm motility. They matched these levels with the ability of the sperm to bind to the zona pellucida in laboratory tests.

Nine out of 16 of the sperm samples from infertile men contained less than 30 per cent of the P34H found in the fertile samples. In each case, these sperm cells could not bind to the zona pellucida.

“We were surprised that we had so many infertile men who lacked the protein,” says Sullivan. Infertility specialists had expected that there would be no single factor that could account for many cases of unexplained male infertility.

The new results, however, suggest that a common theme may be a malfunctioning epididymis which is unable to deposit normal quantities of P34H onto stored sperm. “It points a finger at the epididymis,” agrees John Aitken of the Medical Research Council’s Reproductive Biology Unit in Edinburgh. He would like to see the work repeated with other groups of infertile men to confirm that the problem is as widespread as the Canadian results suggest.

If a deficiency in P34H is confirmed as a major cause of infertility, the protein could be used as a simple diagnostic marker, and the problem might be comparatively easy to treat.

One possible treatment would be to coat P34H-deficient sperm with the protein and mix them with eggs from the man’s partner, in a variant of standard IVF. Before this becomes feasible, however, researchers will have to isolate the gene that codes for P34H, so that large quantities of the protein can be made by splicing the gene into bacteria or cultured cells.

Sullivan and Boué’s work could also lead to new contraceptives. “It might be possible to come up with an inhibitor of P34H in some sort of vaginal cream,” says Erwin Goldberg of Northwestern University in Evanston, Illinois, who is interested in finding ways of blocking the interaction between sperm and egg.

Coronary artery disease is the most serious problem facing heart transplant patients. “It’s a major factor in long-term patient survival and severely limits life expectancy,” says Michael Dunn, one of the researchers at Harefield Hospital. Unlike acute rejection of the organ, which happens within a few months of transplantation and can be managed by immunosuppressive drugs, coronary artery disease develops progressively in the transplanted hearts, and no specific treatments are available. The disease is notoriously diffuse in transplanted arteries, making it untreatable by conventional bypass surgery.

Coronary artery disease begins when damage to endothelial cells lining the inside of the artery triggers a cascade of events at the site of damage. Muscle cells proliferate in the artery wall and fatty compounds build up. Together, these help to cause a dangerous narrowing of the blood vessel. ĐÓ°ÉÔ­´´s believe that in transplant patients, the cascade begins when the immune system recognises transplanted coronary vessels as foreign and attacks their endothelial cells. However, researchers have been unable to identify the proteins in the transplanted vessel that set off this response.

Marlene Rose and her colleagues at Harefield Hospital searched for potential culprits by taking antibodies from the blood of 50 transplant patients and looking to see which endothelial cell proteins they attacked, if any. The researchers found that patients with coronary artery disease were more likely to have antibodies to a protein called vimentin, which is a vital component of the cell’s “skeleton”. The researchers will publish their results in a supplement to the Journal of Heart and Lung Transplantation in November.

Rose says her group is screening more patients to see whether the pattern holds true. If so, anti-vimentin antibodies could provide a simple and cheap way of diagnosing and monitoring the disease in transplant patients. Currently, the only way of detecting the disease is by expensive, invasive techniques such as angiography. Because these techniques run a small risk of causing complications, they are not done in the first year after transplantation, by which time the disease has already taken hold in up to 15 per cent of patients. But why is the immune system even exposed to vimentin, which is normally tucked safely away inside cells?

Rose suggests that previous damage to the endothelium might cause cells to release the protein. “Only a tiny amount of damage is needed to start off the process,” she says, and this could arise during the transplantation itself. Interestingly, vimentin also becomes abundant in the muscle cells of the vessel wall when they are stimulated to divide in the disease. This may be one of the factors contributing to the rapid and diffuse spread of the disease, says Dunn, who suggests that the antibodies may play a role here as well. If anti-vimentin antibodies turn out to be responsible for some of the damage seen in the disease, Dunn believes it may be possible to treat the condition by blocking their activity.

Elaine Perry and her colleagues at the Medical Research Council’s Neurochemical Pathology Unit at Newcastle General Hospital have discovered that sage oil inhibits the enzyme acetylcholinesterase (AChE), which may play a part in memory loss in Alzheimer’s disease.

Progressive deterioration of memory is the main symptom of Alzheimer’s disease. It is accompanied by a drop in the level of the chemical messenger acetylcholine in the brain. Treatments to slow memory loss have focused on AChE, the enzyme which breaks down acetylcholine. The drug tacrine inhibits the action of the enzyme and slows the progress of disease in some patients, but it can have unpleasant side effects, including damage to the liver.

In their search for alternatives, the Newcastle group set out to test whether a number of herbs that are reputed to enhance memory inhibit the action of AChE. “Plants offer a huge resource of varied compounds worth tapping into,” says Jennifer Court, one of the researchers.

Of the 15 herbs the team investigated, sage oil was the most promising. It was effective at blocking the action of AChE in tissue from the part of the brain responsible for memory. Importantly, it did not have a strong effect on a related enzyme.

Before sage can be used as a medicine, the Newcastle group will have to track down the active ingredient. They may then be able to provide a scientific explanation for the belief of the 17th-century herbalist John Gerard, that sage “helpeth a weake braine or memory and restoreth them being decayed in a short time”.

Cells growing in a laboratory culture are living on borrowed time. After a limited number of divisions they become senescent, presumably because they switch on genes that prevent them from dividing any further. Biologists have long assumed that senescence also occurs in the body, contributing to ageing and providing a means of preventing the uncontrolled cell division that causes cancer. But proving this has been impossible, because they did not have a test that could detect senescent cells in the body

Judith Campisi and her colleagues now think they have found one. They started by looking for subtle variations in the internal chemistry of cultured human cells that correlated with the onset of senescence. Eventually they found that senescent skin cells tended to produce an unusual form of the enzyme &bgr;-galactosidase. This enzyme, which removes sugar molecules attached to proteins, is produced in most cells. However, the enzyme produced in senescent skin cells can function under more alkaline conditions. Campisi and her colleagues believe the unusual enzyme is a by-product of senescence, rather than its cause.

A simple staining test can be used to identify cells producing the unusual &bgr;-galactosidase, making it a useful marker for senescent cells. When the researchers applied this test to human skin cells, they found that the amount of altered enzyme they contained increased with the age of the people the cells came from (Proceedings of the National Academy of Sciences, vol 92, p 9363).

The researchers say that the same procedure could be used to test the effectiveness of drugs designed to slow aspects of ageing. “There is tremendous interest in halting the senescence process in skin,” says Glynis Scott of the University of Rochester, New York, who worked with Campisi on the project.

Campisi believes that the discovery of a test for senescent cells will also help in the search for genes which inhibit cancer. The test could pin down genes that turn on the biochemical mechanisms that lead to senescence, and so stop tumour cells dividing.

Across much of the tropics, the parasite, Plasmodium falciparum, is becoming resistant to drugs such as chloroquine. Until now, most scientists studying the problem have focused on the effects of different patterns of drug use. But Karen Day and Rick Paul of the University of Oxford say that the speed with which drug resistance spreads also depends on the parasite’s mating strategy. When P. falciparum inbreeds, they say, resistance spreads more quickly.

P. falciparum mates once during its life cycle, inside its mosquito vector. The mosquitoes suck up male and female parasite cells from an infected human, which then fuse with one another. These sex cells can come from the same or different strains, allowing the parasite to inbreed or crossbreed.

Working with researchers at the Papua New Guinea Institute of Medical Research, Day and Paul dissected 16 000 mosquitoes to study the occurrence of inbreeding and crossbreeding in the malaria parasites of Papua New Guinea, and compared their results with a similar survey in Tanzania conducted by David Walliker of the University of Edinburgh. “We knew there was a difference in transmission of the parasite and had indications that the breeding pattern was different,” says Day.

The researchers looked at three P. falciparum genes which each vary from strain to strain. In Papua New Guinea, 85 per cent of all matings were between parasites of the same strain (Science, vol 269, p 1709). In Tanzania, Walliker had found that only 35 per cent of the parasites were inbred.

Day says that these different mating patterns are largely due to the different rates of parasite transmission in the two countries. Tanzanians suffer ten times more mosquito bites than people in Papua New Guinea and as a result carry more different strains of parasite.

The researchers argue that their results help to explain why resistance to chloroquine has spread more slowly in Tanzania than in Papua New Guinea. Drug resistance involves mutations in several different genes, says Day. Crossbreeding is important in bringing these genes together in the first place, but if it is too common, the genetic shuffling of sexual reproduction could separate the key genes once more. If the parasites inbreed, however, resistance genes can spread more rapidly through the population.

Tumours develop from cells where the genes that control cell division have mutated. The mathematical models focus on mutations in two types of genes: those for making growth factors – proteins that trigger cell division – and those needed to make receptors on cell surfaces which are activated by growth factors. Using their models, Sherratt and Nowak found that in cells carrying both mutations, tumours develop rapidly and contain both normal and mutant cells – just as in real tumours.

Sherratt believes that this analysis may be useful for treating breast cancer. “We’re trying to interest people in it,” he said. At the moment, doctors count the number of receptors on a breast cancer cell and use it to predict how serious the tumour is and what type of surgery is needed. But this decision is largely subjective. Sherratt thinks that his model could provide a surer basis for deciding which treatment to use because it gives a more precise measure of how the tumour will develop.

The notion that astigmatism distorted El Greco’s vision, and that the stretched figures he painted appeared normal to him, has been around since early this century. According to this school of thought, Holbein, who painted broad, squat figures, might also have been afflicted with astigmatism, although in his case it would have had to stretch images vertically.

However, many people have disagreed with this analysis of El Greco’s style, arguing that the distortions he saw in his sitter and his painting would have cancelled each other out. Anstis decided to put the astigmatism theory to the test. “Why calculate what you can observe experimentally?” he asked.

Anstis reproduced El Greco’s supposed astigmatism in a group of volunteers by covering one eye and fitting the other with a monocular that stretched the image horizontally. He found that when they were asked to draw squares freehand they drew vertically elongated rectangles, but when shown a square they copied it perfectly.

Anstis then persuaded one of his volunteers to wear the monocular for four days to see if people could adapt to the artificial astigmatism. “After a few days, she acted as if she had normal vision,” he said. “The freehand squares started off as tall, thin rectangles, but became squarer every day.”

Astigmatism is a common visual defect caused by distortion of the cornea. It affects around 80 per cent of the population, though usually only in a very mild form. Opticians can correct it with glasses that cancel out the distortion.