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By Stephen Luntz

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Breast Cancer Linked to Calcium Pump
A misbehaving calcium transporter has been linked to certain types of breast cancer. The discovery offers hope for better treatment of these cancers, with indications that related transporters may be relevant in other cases.

The SPCA2 pump normally forces calcium into a section of the cell known as the Golgi complex. However, A/Prof Greg Monteith of the University of Queensland, along with colleagues there and at Johns Hopkins University, found that the SPCA2 protein is present in large quantities in many breast cancers.

“In breast cancer cells, the pump sits not on the Golgi complex but on the membrane surface and turns on the calcium channel, letting calcium into the cell,” says Monteith.

“SPCA2 belongs to a family of proteins related to transporters we already have drugs for, so it is what we call a druggable target,” Monteith adds, offering hope for new treatments from the research. Moreover, the team has identified other calcium transporters that may play similar roles in other forms of breast cancer.

“We are focusing on those breast cancer types that have the poorest prognosis,” Monteith says.

The research was published in Cell.

The Source of Sperm
The protein FGF9 is essential to sperm production, according to research at the University of Queensland. The finding follows the discovery by the same research team that retinoic acid, a derivative of vitamin A, triggers the production of ova.

“It sounds obvious that men produce sperm and women produce eggs,” says Dr Jo Bowles of UQ’s Institute for Molecular Bioscience. “But sperm and eggs start out as identical cells, and it’s only through a complex process of signals that these cells end up as sperm in men and eggs in women.”

The processes begin during embryonic development, and the wrong chemical signals can lead to infertility or cancer later in life.

Following their previous discoveries with retinoic acid, Bowles and Prof Peter Koopman were keen to discover whether the absence of retinoic acid makes germ cells turn into sperm, or if some other trigger is required.

FGF9 is active in the embryonic male gonad at the time when sperm development begins, making it an obvious candidate to trigger sperm development. Studies on mice that either lack FGF9 or have abnormally high FGF9 production indicate that the guess was right.

“It now appears that whilst retinoic acid pushes reproductive cells towards developing as eggs, FGF9 opposes this process and drives them towards becoming sperm,” Dr Bowles said. “It means there is a failsafe built into the system. If a female is lacking retinoic acid, it doesn’t mean her reproductive cells will develop into sperm because she won’t have FGF9 to trigger spermatogenesis.”

The research was conducted using mice but Koopman says that “these sorts of mechanisms seem to be quite well-conserved evolutionarily, and particularly between humans and mice. There is human evidence for retinoic acid’s role, so it is likely this applies to humans as well.”

The processes involved occur so early in human development that Koopman doubts that the discovery could be used to reverse infertility. However, he thinks it may improve IVF and be useful for fighting testicular and ovarian cancers, which may sometimes be caused by mixed chemical signals at this stage of development.

Koopman also believes that there may be prospects for using the research to control fertility in pest species.

Did Ancient Aborigines Reach America?
Claims that Australian Aborigines, or their close relatives, were the first inhabitants of South America have been criticised for lack of sufficient evidence. While the theory received widespread coverage in the Australian media in October, two leading Australian palaeoanthropologists are far from convinced.

The claim made by Dr Walter Neves of the University of Sao Paulo is based on skulls dated to 11,000 years ago. “The results suggest a clear biological affinity between the early South American and the South Pacific population,” Neves said in an interview with Cosmos.

Native Americans migrated across the Bering Straight 10,000 years ago, forming what is known as the Clovis culture. Modern cranial features, fossilised skull shapes and DNA evidence all point to a close relationship with East Asian populations.

However, occasional reports have been made of even older American fossils with different facial features, suggesting that at some stage people with a different ancestry reached the Americas, either by the same or a different route.

In the 1970s a female skeleton was found in a cave in Central Brazil, and named Luzia. Charcoal deposits around it have been used to date Luzia to 11,000–14,000 years ago. Examination of this important find, and many others, stalled because the leader of the team who found it died shortly afterwards and the other members fought to the point of disbanding.

Neves examined Luzia and other remains found nearby in the late 1990s. In 2005 he published a paper in the Proceedings of the National Academy of Science using evidence from multiple sites to support his claim of a previous wave of migration into the Americas.

While the idea that a separate population occupied the Americas before modern Native Americans would be enormously significant for palaeoanthropology, Cosmos made the much more radical claim that this pre-Clovis population may have been related to Aborigines, based on the shape of Luzia’s skull. “I was amazed to walk around the reconstruction of Luzia’s skull, which clearly looked Aboriginal, and yet realise this was found a world away and was so very ancient,” Cosmos Deputy Editor Jacquie Hayes said in a media release.

However, Prof Peter Brown, who is Chair of Palaeo­anthropology at the University of New England, is not convinced by this claim. “All terminal Pleistocene crania around the world tend to look Australoid in some respects, particularly those from the warmer parts of the globe,” he told Australasian Science. “Longer and narrower skulls, more bony reinforcement, larger teeth and more projecting faces. You could make the same claim for Mesolithic skulls from anywhere.”

Colin Groves, who is Professor of Bioanthropology at the Australian National University, added that Neves’ studies “are convincing that these early people in the New World are not like today’s people that we consider ‘Native Americans’. They are less convincing that they were Australoid, let alone actual ‘Australian Aborigines’.”

Groves says that some of the features said to match Aborigines are actually universal to humans, while distinctly Aboriginal features are lacking in the early Brazilian skulls he has seen.

Groves also notes that “one has to be careful” in interpreting the shape of human skulls, as some show evidence of artificial cranial deformation – a point also made by Brown last month over claims of an evolutionary connection between Pleistocene Australians and Indonesian Homo erectus (AS, November 2010, pp.18–21).

Introduce Eggs to Infants
Parents who try to protect their children from allergies by delaying the introduction of foods that frequently produce reactions may be making things worse, at least in the case of eggs.

A/Prof Katie Allen and PhD student Jennifer Koplin of the University of Melbourne compared the outcomes in 2500 Victorian children. Within the sample some children were introduced to eggs at 4–6 months, while other parents waited until their children had their first birthday.

By 14–18 months, those who first encountered eggs after 12 months had three times the allergy rate than those who were given eggs early. “Our study suggests that babies who ingest these foods at an earlier age may be less likely to develop food allergies as they grow older,” Allen says.

Allen recommends giving children cooked eggs, as small amounts in cakes or biscuits appeared to have no protective effect.

Two other studies have produced similar findings for wheat and peanut allergies, but Koplin says that one study was very small and the other had design problems. Nevertheless, these still amounted to more evidence in favour of early introduction than exists against it.

Koplin also says she can find no published evidence for benefits arising from a late introduction to allergenic foods. Despite this she notes: “Until recently, Australian and international guidelines recommended that infants with a family history of allergy delay introducing allergenic foods such as egg, peanut and nuts until up to 2–3 years of age”.

Some parents may put off giving children allergenic foods on the basis that reactions will be less frightening in older children. However, Koplin says that “anaphylaxis is just as scary in a 12-month-old as a 6-month-old”.

Other infant allergic reactions to eggs include hives, vomiting and diarrhoea. However, unlike peanut allergies, children usually grow out of these as they age.

“Probably the reason parents started delaying giving children foods was that there were more allergies around,” Koplin says. “So it is unlikely delays are the sole reason. However, it could be a contributing factor” to the recent rise in allergy rates.

Stroke Risk from Neck Manipulation
Neck manipulation techniques that have been linked to stroke are no more likely to hasten recovery than safer alternatives, a study has found.

Dr Andrew Leaver of the University of Sydney’s Faculty of Health Sciences compared 182 people who had recently suffered neck pain for the first time or had a recurrence after at least one pain-free month. The patients were given either neck manipulation using rapid thrusting movement of the spine to produce audible clicks, or mobilisation using slow oscillating movements of the neck joints.

All treatments were performed by qualified physiotherapists or osteopaths. Other treatments were allowed, such as exercise and advice on behavioural modification.

Circumstances were assessed at the start of the trial, when treatment ceased and 3 months later. Both treatments produced successful outcomes in reducing pain and disability. “In fact, it was surprising how similar the two treatments were on all measures,” says Leaver.

“Neck manipulation is a highly controversial treatment as there are published studies that demonstrate an increased risk of stroke in patients that receive neck manipulation,” Leaver says. “This appears to be a rare occurrence, and there is still some debate about whether manipulation can cause stroke.”

However, Leaver notes: “It makes us question why patients or practitioners would favour a treatment which possibly carries risk of catastrophic outcome over an equally effective one with very few reported complications despite widespread use.”

Leaver says that there is no reason to believe the process of clicking one’s own neck, common among sufferers of neck pain, is a risk. “It doesn’t seem to be the clicks that cause the stroke, but the thrusting motion that causes the click in this sort of manipulation.”

The research was published in the Archives of Physical Medicine and Rehabilitation. Patients with whiplash were excluded, as Leaver says these cases are considered a clinically different condition.

Men Unaware of Osteoporosis
One-quarter of Australian men over the age of 70 meet one of the Pharmaceutical Benefits Scheme’s (PBS) criteria for osteoporosis treatment, according to a study published in the Medical Journal of Australia. However, 90% of them did not realise they had the condition, putting them at greater risk of hip fractures or other bone injuries.

“Identifying men who will benefit from osteoporosis treatment, and increasing the proportion of eligible men receiving appropriate treatment, is a public health issue,” says Kerrin Bleicher, a PhD student at the Sydney Medical School. “Currently it is projected that, because of the ageing population, hip fractures may double by 2026 and increase fourfold by 2051.”

The PBS subsidises osteoporosis treatments for patients with minimal trauma fractures, vertebral deformities or low bone mineral density.

Many women are not treated for osteoporosis symptoms, but this research on 1705 men in NSW suggests that the problem is even more common in men, even though fractures in men produce higher rates of mortality and increased morbidity than in women.

Kelp’s Southern Ocean Journey
Large amounts of bull kelp cover New Zealand’s beaches, and it has long been hypothesised that it can travel between distant islands and even continents. Now a new study has found that bull kelp acts like a Southern Ocean ferry, enabling many species of animals to make their way around the Southern Ocean.

Genetic analysis of kelp from different islands has previously produced evidence that the Southern Hemisphere’s last ice age was colder than previously thought (AS, June 2000, pp.23–25). However that research, by Dr Ceridwen Fraser of the University of Otago, was based on the assumption that kelp could survive long enough at sea to make interchange possible.

Now Fraser and A/Prof Jon Waters of the University of Otago have supported this claim with the discovery of bull kelp on Dunedin’s St Clair Beach whose genetics indicate that it originated from islands up to 600 km further south.

“We see a lot of bull kelp drifting out at sea, and scientists have always suspected that it could travel a long way, perhaps even crossing entire oceans. Now we know it really can,” Fraser says.

Given this exchange it might be expected that bull kelp populations would be genetically identical around the Southern Ocean, but many locations have highly distinctive genetics. Fraser believes this is because a travelling kelp branch is unlikely to breed with the locals as “the males and females are joined at the hip”.

A single plant will also struggle to establish itself against the much larger local population. “However, if a lot of territory has been cleared off by ice scour or a really big storm, a new arrival may be able to colonise some space and establish itself,” Fraser says.

Many species of animals live deep within the kelp and are able to survive long journeys. Species that have caught a ride include snails, sea stars, crustaceans and sea spiders. All of these live within the kelp on its normal rocky habitat.

Some species, such as goose barnacles, avoid kelp while it is onshore but colonise it while it floats. The size of the barnacles indicates how long kelp has been afloat.

Fraser admits that a 600 km journey does not prove that kelp can survive the year it would take to voyage from New Zealand to South America, but regards the finding as a significant step to demonstrating that bull kelp acts like a natural cruise liner, rafting populations around the southern seas.

Antibody Reorganises Anthrax Toxin
An antibody against the anthrax toxin reorganises the proteins that make up the toxin to prevent them from affecting the body. This sort of reorganisation has never been observed before, but may be used by antibodies against other poisons and diseases.

“The anthrax toxin is made up of multiple proteins and only becomes active – and starts doing damage – when those proteins cluster together in a very specific way,” says team leader A/Prof Alok Mitra of the University of Auckland.

While most antibodies link into points on the antigen, Mitra’s students found one antibody that adds more proteins to the cluster and causes larger groupings to form, preventing the toxin from entering cells.

“Our research was the first to show that an antibody can structurally alter its target in this way, but it is unlikely to be the only example in nature and may in fact prove to be an important biological process,” says Mitra.

The discovery could be useful for finding similar antibodies, indicating it might be helpful to look for examples where toxins group together harmlessly. By understanding how the antibody works it may also lead to more effective vaccines.

Mitra says the discovery was a complete surprise. “When my students told me about it I didn’t believe it. I expected the antibody would operate similarly to other antibodies.”

Genetic Link to Migraine
A gene whose faults lead to certain migraines has been identified. The TRESK protein regulates pain pathways and the threshold of sensitivity of pain centres in the brain. However, a faulty version of the KCNK18 gene prevents TRESK from functioning.

“For the first time we have found a clear inheritance pattern for this gene defect and know it is the cause behind this debilitating condition,” says Prof Lyn Griffiths, Director of the Griffith Health Institute.

Previous studies have found genes that increase the risk of susceptibility to migraines, but in one large family studied by researchers at the University of Montreal every person with one form of the KCNK18 gene suffered migraines while every person with the normal form did not.

The Australian contribution to a Nature Medicine paper was to seek the gene in 500 people who were not from that family as well as 500 controls. Griffiths says that only ten people in their sample had the genetic variation, suggesting that while it is causative, it is not common. Moreover, some people with the defective gene were not prone to migraines, indicating that other genes can interact with it.

Griffiths believes that there are three different classes of genes implicated in migraines. Some of these are vascular, such as the MTHFR gene previously identified by Griffiths (AS, March 2010, pp.29–31). Other genes are hormone-related, while KCNK18 is an immunotransmitter gene.

Unfortunately, Griffiths doubts that KCNK18-induced migraines will be as easy to treat as those caused by MTHFR, where additional folate in the diet has produced spectacular results. “Ion channels are more complex, and there are no known cofactors for TRESK,” Griffiths says. “We are looking for things that might stimulate its function, but we don’t know of any yet.”

Fish Dads Do a Swimmer
Cichlids are common in African and South American rivers and lakes. While most fish leave their eggs and fry to fend for themselves, all of the more than 1000 known species of cichlid care for their eggs and larvae, and some also nurture the fry.

Among Nicaraguan cichlids, both parents usually protect the eggs and larvae from predators and subsequently produce mucus for the young to feed on. Each parent contributes equally to feeding and protecting the offspring for several weeks after the eggs are laid.

However, in some cases the father abandons the offspring to seek other mates while the mother maintains her guard. An international team including Dr Bob Wong of Monash University’s School of Biological Sciences set out to find out when this happens – and the consequences. “Being deserted by their mate is bad news for the abandoned female cichlid fish and her young brood,” says Wong.

The females made as many charges against potential predators as an intact couple, but they were unable to protect the same amount of territory, possibly because they were less likely to see intruders until they were dangerously close to the young. Moreover, the extra effort involved left the females in poorer condition.

Comparisons of different species found that larger cichlid males were more likely to desert the nest. Wong thinks this is probably because the females of larger species have a better chance of protecting the young on her own, so male deserters have reasonable prospects of passing on their genes twice. Desertion was also more common later in the season, when the father might have done just enough to ensure that the young survive.

In mammals it is assumed that females are more likely to care for their young as they can be certain that the offspring are their own. However, this may not be the case with fish, where male care is as common as female care among non-cichlid species. Wong hopes that the study will shed light on such issues across the animal kingdom.

Fine Structure Depends on Where You Look
One of the fundamental constants of the universe may not be constant, with measurements of the fine structure constant showing it is slightly different in distant galaxies. More surprisingly, the variation depends on the direction in which you look.

The fine structure constant (α) is equal to the charge of an electron squared (e2), divided by the Plank constant (h) multiplied by the speed of light (c), or α = e2/hc. All three are important physical constants. For the fine structure constant to change at least one of these must also be varying.

The idea that the fine structure constant might vary is not new. Dr John Webb of the University of NSW and Swinburne’s Dr Michael Murphy found evidence to suggest that the value of α was slightly lower when light from very distant quasars passed through gas in somewhat less distant galaxies where the absorption spectral lines are determined by α (AS, March 2006 p.13).

Surprising as it was to find a fundamental constant being variable, the results were consistent with certain models of the early universe. However, when Webb, Murphy and others used a second telescope to check their results they found something even less expected.

“The Keck telescopes and the Very Large Telescope are in different hemispheres – they look in different directions through the universe. Looking to the north with Keck we see, on average, a smaller alpha in distant galaxies, but when looking south with the VLT we see a larger alpha,” says Julian King of the University of NSW. The variation is just one part in 100,000.

“After measuring alpha in around 300 distant galaxies, a consistency emerged: this number, which tells us the strength of electro­magnetism, is not the same everywhere as it is here on Earth, and seems to vary continuously along a preferred axis through the universe,” Webb says.

Galaxies lying in a plane perpendicular to this axis give values of α that are indistinguishable from the value on Earth in both telescopes, making instrumental error unlikely. Measurements were taken as far as 12 billion light years, and the rate of change of α appears to be linear with distance.

The researchers are fully aware that extraordinary claims require extraordinary evidence, and are in the process of both reanalysing their data and seeking further results. A paper is undergoing peer review for Physical Review Letters, and a preliminary version posted online set off a storm of discussion on science blogs and overseas media.

Webb says that “we don’t really have any information” about which of the constants would be responsible for the change, and is not sure if it would be possible to test this.

It’s not clear if an observer transported to a galaxy where α differs by one part in 100,000 would notice any difference. “For star formation to be different, α would probably have to change quite a lot,” Webb says. The changes to our understanding of the universe, however, are far more profound if the work is confirmed.

While Webb suggests that “one could have a scalar field coupled to the fine structure constant, with variations in that causing spatial or temporal variations,” he does not know what might cause variations in such a field.