Short-term exposure to low levels of particulate air pollution may increase the risk of stroke or mini-stroke, according to findings that suggest current exposure standards could be insufficient to protect the public.”The vast majority of the public is exposed to ambient air pollution at the levels observed in this community or greater every day, suggesting a potentially large public health impact,” said Lynda Lisabeth, lead author and assistant professor in the University of Michigan School of Public Health.

However, Lisabeth stressed that the association requires further study in other areas with varying climates and alternative study designs. Stroke is the third leading cause of death in the United States.

The study examined particulate air pollution in a southeast Texas community where there is a large petroleum and petrochemical industry presence. Particulate matter is one type of air pollution, defined as tiny particles of solid or liquid that can cause numerous health problems when inhaled. These particles can be man-made or from natural sources.

In the study, researchers identified ischemic strokes and transient ischemic attacks (TIA), sometimes called mini strokes but that often lead to a stroke later. Ischemic attacks are caused by a blockage of blood flow to the brain by a blood clot.

The results showed borderline significant associations between same day and previous day fine particulate matter exposures and ischemic stroke/TIA risk. Similar associations were also seen with ozone, another type of pollution. Despite the fossil fuel industry in the area, fine particulate matter exposures were low relative to other regions of the country, probably because of the proximity to the coast and prevailing wind patterns.

Findings suggest that recent exposure to fine particulate matter may increase the risk of ischemic cerebrovascular events specifically. Some research has shown that particulate air pollution is associated with acute artery vasoconstriction and with increased thickening of the blood, which may enhance the potential for blood clots. However, this requires further study.

Researchers looked at data from the Brain Attack Surveillance in Corpus Christi Project, a population-based stroke surveillance project designed to capture all strokes in Nueces County, Texas. Ischemic stroke and TIA cases between 2001 and 2005 were identified using trained staff and later verified by neurologists. Daily historical air pollutant and meteorological data were obtained for the same time period from the Texas Commission on Environmental Quality’s Monitoring Operations database. Data on fine particulate matter and ozone were available from a centrally located monitor in Corpus Christi, Tex., located upwind of the local industrial facilities. The majority of stroke/TIA cases were also located upwind of local chemical plants and refineries.

When a corporation has a public relations crisis, the news media splash photos of the company’s CEO around the world. According to new research in the Journal of Consumer Research the shape of the CEO’s face evokes judgments about the person and the situation.

“A company can control what face is put on the crisis, and [our] research suggests that the face shape of this person is not a trivial consideration,” say authors Gerald J. Gorn, Yuwei Jiang (both Hong Kong University), and Gita V. Johar (Columbia University).

In the study, participants examined news accounts of fictitious corporate misdeeds. The research found that in a minor public relations crisis, participants held a more favorable attitude toward a baby-faced CEO (large eyes, small nose, high forehead, and small chin) than a mature-faced CEO. The study subjects perceived baby-faced CEOs as more honest.

However, when the situation was more serious, and especially when it involved questions of competency, a baby-faced representative didn’t help the company. “In contexts where innocence conveys naïveté, a mature face is evaluated more favorably,” write the authors. For example, if a company failed to detect important defects in products, the baby-faced CEO was perceived to be detrimental.

The research also found that the “baby-face effect” is unconscious, and that when participants were distracted (by memorizing a number) the babyface had greater influence. The unconscious nature of baby-face effects has not previously been shown in other research. The authors also demonstrate that the association between baby-faced people and honesty can be overcome by showing participants pictures of supposed criminals with babyfaces.
So, what advice do the authors give?  “While there is no panacea for a company suffering a PR crisis, putting the right face on a response might just help save some face.”

“Consumers who understand their emotional ability can make higher quality consumption decisions such as health decisions and product choices,” explain the authors, Blair Kidwell, David M. Hardesty, and Terry L. Childers (University of Kentucky). “A person can know a lot about nutrition and know what foods are not healthy, but can still make poor decisions when unable to recognize, reason, and solve problems based on emotional patterns,” they add. For example, compulsive eaters may understand nutrition, but they may not realize their emotions affect their food choices.This research establishes a new method for assessing consumers’ emotional intelligence. The authors developed a scale by testing undergraduates with more than 110 questions about emotions and consumption. As a result of this research, the authors were able to determine which emotion-related questions best predicted overeating.

The researchers then narrowed the questions to 18. They measured four different dimensions of consumer emotional ability: perceiving, facilitating, understanding, and managing emotions.  This 18-item scale—called the CEIS, or Consumer Emotional Intelligence Scale—is a highly reliable indicator of consumer behavior.

It seems consumers who care about healthy eating need to consider their feelings instead of studying nutrition labels.

Researchers at the Burnham Institute for Medical Research, led by Josh Luis Millhn, Ph.D., have demonstrated in mice the first successful use of enzyme replacement therapy to prevent hypophosphatasia (HPP), a primary skeletal disease of genetic origin. This discovery lays the foundation for future clinical trials for HPP patients.

Rickets is a softening of the bones that most commonly results from a lack of vitamin D or calcium and from insufficient exposure to sunlight. Hypophosphatasia is a rare, heritable form of rickets caused by mutations in a gene called TNAP, which is essential for the process that causes minerals such as calcium and phosphorus to be deposited in developing bones and teeth. The physical presentations of this disorder can vary depending on the specific mutation, with more severe symptoms occurring at a younger age of onset. The most severe form of the disease occurs at birth, which can present with absence of bone mineralization in utero, resulting in stillbirth.

Using a mouse model, Josh Luis Millhn, Ph.D. tested the hypothesis that, when administered from birth, a bone-targeted form of the TNAP gene would ease the skeletal defects of HPP. The Millhn laboratory, in collaboration with scientists from Enobia Pharma in Montreal, Canada and from the Shriners Hospitals for Children in St. Louis, Missouri, created a soluble form of human TNAP that had been shown to display a strong attraction to bone tissue. Upon injecting the enzyme into the fat layer under the skin of the mice, the treated mice maintained a healthy rate of growth and apparent well being, as well as normal bone mineral density (BMD) of the skull, femur and spine. In fact, complete preservation of skeletal and dental structures were observed after 15 days, and bone lesions were still not seen after 52 days of treatment.

“While the biochemical mechanism that leads to skeletal and dental defects of HPP is now generally understood,” said Dr. Millhn, “there is currently no established medical treatment.”

Given the success of this therapy in preventing HPP, current efforts in Dr. Millhn’s laboratory are focused on reversing the bone defects in mice once the disease is quite advanced. Future clinical trials may reveal this as the first promising therapy for patients with this genetic disorder.

Viruses are true experts at importing genetic material into the cells of an infected organism. This trait is now being exploited for gene therapy, in which genes are brought into the cells of a patient to treat genetic diseases or genetic defects. Korean researchers have now made an artificial virus. As described in the journal Angewandte Chemie, they have been able to use it to transport both genes and drugs into the interior of cancer cells.

Natural viruses are extremely effective at transporting genes into cells for gene therapy; their disadvantage is that they can initiate an immune response or cause cancer. Artificial viruses do not have these side effects, but are not especially effective because their size and shape are very difficult to control—but crucial to their effectiveness. A research team headed by Myongsoo Lee has now developed a new strategy that allows the artificial viruses to maintain a defined form and size.

The researchers started with a ribbonlike protein structure (β-sheet) as their template. The protein ribbons organized themselves into a defined threadlike double layer that sets the shape and size. Coupled to the outside are “protein arms” that bind short RNA helices and embed them. If this RNA is made complementary to a specific gene sequence, it can very specifically block the reading of this gene. Known as small interfering RNAs (siRNA), these sequences represent a promising approach to gene therapy.

Glucose building blocks on the surfaces of the artificial viruses should improve binding of the artificial virus to the glucose transporters on the surfaces of the target cells. These transporters are present in nearly all mammalian cells. Tumor cells have an especially large number of these transporters.

Trials with a line of human cancer cells demonstrated that the artificial viruses very effectively transport an siRNA and block the target gene.

In addition, the researchers were able to attach hydrophobic (water repellant) molecules—for demonstration purposes a dye—to the artificial viruses. The dye was transported into the nuclei of tumor cells. This result is particularly interesting because the nucleus is the target for many important antitumor agents.

A puzzling medical condition, identified more than 2,000 years ago by Hippocrates, has finally been explained by researchers at the University of Leeds.The phenomenon of “finger clubbing”, a deformity of the fingers and fingernails, has been known for thousands of years, and has long been recognized to be a sign of a wide range of serious diseases – especially lung cancer.

“It’s one of the first things they teach you at medical school,” explained Professor David Bonthron of the Leeds Institute of Molecular Medicine. “You shake the patient by the hand, and take a good look at their fingers in the process.”

Lung cancer, heart disease, hyperthyroidism, various gastrointestinal diseases and many other conditions all result in finger clubbing. But exactly why swollen, reddened fingers should be an indicator of serious illness has remained a mystery – until now.

“There are benign cases of clubbing, where it isn’t associated with other illnesses, but particularly because of the link to lung cancer, it is generally regarded as rather sinister,” said Bonthron. “You look at the range of conditions connected to finger clubbing and wonder what on earth they could have in common.”

The researchers found clues in the medical literature, detailing past cases and previous research. “We knew that in cystic fibrosis patients who have undergone a lung transplant, their finger clubbing goes away. The same goes for empyema patients who have had their lungs drained. It suggested that impaired lung function was somehow crucial to finger clubbing – but we didn’t understand how.”

Prof Bonthron, Dr Chris Bennett of the Yorkshire Regional Genetics Service and their colleagues studied a group of patients suffering from inherited primary hypertrophic osteoarthropathy (PHO), a genetic disorder in which the finger clubbing is accompanied by painful joint enlargement and a thickening of the bone.

Their findings implicated a fatty compound called PGE2, which is produced naturally by the body to mediate the effects of internal inflammation. Crucially, once it has done its work, PGE2 is broken down by an enzyme 15-HPGD, produced in the lungs. The patients followed by the Leeds study were found to have a genetic mutation which prevented the production of 15-HPGD, resulting in up to ten times as much of the PGE2 in their systems.

“If you don’t have this enzyme the PGE2 isn’t broken down normally and simply builds up,” said Bonthron, whose findings are published online this week in Nature Genetics.

In lung cancer patients, it is most likely overproduction of PGE2 by the tumour that causes the clubbing. In congenital heart disease, blood bypasses the lungs, where PGE2 is normally broken down by 15-HPGD.

The researchers have suggested that a straightforward urine test for levels of PGE2 may be a useful first step in the diagnosis of individuals with unexplained clubbing, and to understanding whether it is the symptom of something far more serious. The results also suggest that existing drugs such as aspirin, which are already used to prevent PGE2 production, may be effective in reducing the painful symptoms of finger clubbing.

It has taken 2,000 years to make the connection, but Bonthron adds: “Actually, when you look back, it’s rather obvious. When we found this gene, everything else fell neatly into place – it was like a smack on the forehead.”

Fishermen hold empirical knowledge that tuna aggregate under floating objects, such as lengths of old rope, pieces of wood, or even large marine mammals. There is still no full explanation for this aggregation behaviour, but the past 20 years have seen purse-seine fishery operators take advantage of the associated concentrations of fish. Fishermen cast off floating rafts equipped with buoys which act as FADs. An enormous purse-seine net, deployed in a wide arc on either side of the vessel, encircles the school of tuna that come to shelter under the FAD. The lower part of the net is tightened, enclosing the fish in a hemisphere large enough to entrap a mass of tuna.

A sudden growth in the size of tropical tuna catches taken from under these artificial drifting objects was observed for the early 1990s. This was true especially for juveniles. Between 1996 and 2005 the average annual catch taken on FADs reached 1 115 000 tonnes, nearly a third of the global figure for tuna, all species considered together. In Japan, the fish processing industry furthermore had long reported that the flesh from floating-object associated tuna was less plump than that of specimens caught from free schools. This prompted an IRD research team to investigate whether or not the practice of drifting FAD fishing could set up an ecological trap for the tropical tuna species.This trap concept is a notion from population biology used to describe situations in which the population falls following a sudden change in its environment, most often linked to human activity. An example is give by marine turtles which, after hatching on beaches, use the sparkle of moonlight on the sea surface to guide themselves back to the ocean. However, high light pollution levels on urbanized coastlines in certain regions disturbs their sense of direction. Young turtles therefore set off on a path that leads them to land, where they die from dehydration.

Over the past ten years, over 30% of world catches of skipjack (Katsuwonus pelamis), bigeye (Thunnus obesus) and yellowfin (Thunnus albacares) tuna, the three tropical tuna species which can be caught at drifting FADs, have been achieved using this fishing method. For the skipjack amounts taken under drifting FADs reached even as high as 72% of all catches. To check if the large-scale deployment of drifting FADs could present an ecological trap for these species, a range of biological (fish plumpness, growth rate, stomach fullness) and ecological (migration pattern and distance) indices were determined on yellowfin and skipjack captured under FADs in the Atlantic and Indian Oceans. Comparison was then made with data gathered from free-school caught individuals of these same species. A salient finding was that 74% of drifting FAD-associated skipjack had empty stomachs at the moment of capture compared with only 13% for those fished from free schools. Figures of the same order of magnitude were obtained for yellowfin, with proportions respectively reaching 49% caught on drifting FADs and 7% from free schools. The survey indicated that the tuna caught under the FADs fed less well than those fished from free schools. Moreover, the fact that for the same weight the FAD-associated specimens caught showed lower plumpness than the free-school ones could reflect a deficiency in energy-reserve accumulation in those that concentrated around the floating devices.

The research team also sought to find out if the large-scale deployment of drifting FADs could affect the migration patterns of these far-travelling fish species. Tagging surveys allowed comparison of the nature of migrations accomplished by fish moving with the drift of FADs with that of non-FAD-associated individuals. The migration directions and displacement rates in terms of daily distances travelled were indeed affected by the presence of artificial floating objects. Drifting FADs therefore appeared to act as super-stimuli, like strong magnets exerting a binding attraction that leads the tuna towards ecologically inappropriate waters with scarcer food supplies. This survey brought support for a body of reasonable assumptions regarding the tuna behaviour. However, it did not provide certain confirmation of drifting FADs’ negative impact on the entire life cycle of these tuna species and therefore of their possible role as a true ecological trap. Nevertheless, the biological effects observed indicated that it would be more reasonable to preclude deployment of drifting FADs near coasts where tuna juveniles aggregate. These young fish represent the future of the whole stock and such a restriction would be a way of avoiding their being led astray, away from the zones which are ecologically most favourable to them.

New genetic mutations responsible for impaired fetal movement, which leads to a multitude or problems in later life as well as early spontaneous abortion, have been identified by a group of scientists, the annual conference of the European Society of Human Genetics will hear tomorrow (Saturday 31 May). Dr. Katrin Hoffmann, of the Charité University Hospital, Berlin, Germany, will say that her team’s findings could lead to strategies to prevent multiple miscarriages, and for children born with fetal akinesia deformation sequence (FADS) due to impaired fetal movement in the womb.FADS is a frequent genetic condition, affecting about 1 in 3000 pregnancies, and manifests itself in a number of ways – growth retardation, fetal hydrops (abnormal accumulation of fluid in the fetal organs), pulmonary hypoplasia (incomplete development of the lungs) and joint contractures. Studying a family in Oman with four affected children, and a history of multiple abortions, the scientists identified for the first time a genetic mutation on chromosome 2 which appeared to be implicated.

“The children in the family had contractures, a curved spine, and skin webbing” says Dr. Hoffmann. “When we carried out the genetic mapping we identified a mutation that encodes one of the sub-units of the acetylcholine receptor (AChR). Acetylcholine is a neurotransmitter; it transmits signals from nerve to muscle, enabling an individual to move. The genetic changes we found seriously disrupt the functioning of this receptor, meaning that the fetus cannot move properly in pregnancy.” Such a defect has multiple effects, since normal fetal movement is essential for normal fetal development and growth.

The scientists sequenced DNA from 75 patients with severe FADS and found that not all of them had mutations in the gamma sub-unit of the AChR. Reasoning that other components of the AChR pathway might be affected, they tested additional genes and found disease-causing changes there. “It has previously been shown that milder mutations in the AChR pathway cause myasthenic syndrome, a form of muscle weakness that starts later in life”, says Dr. Hoffmann. “But until now we did not know that the same genes could have such an impact on the prenatal development of a baby.”

The scientists intend to continue testing for FADS diseases, and to look at other genes of the AChR pathway, which they believe may hold the clue to the disease in other families. “The AChR pathway is one of several possible causes of the disease group, and we want to distinguish the different causes and to study other pathways in collaboration with existing specialist teams”, says Dr. Hoffmann.

Dr. Hoffmann and her team believe that their work will be important for genetic counselling of families with multiple spontaneous abortions or prenatal death of the baby. “In addition, some of the babies born with contractures and breathing problems could benefit from medication such acetylcholine esterase inhibitors, currently used for the treatment of myasthenia gravis and inherited myasthenic syndrome, she says.

Awareness of the condition could be life-saving. In one of the families studied, both affected children had contractures and breathing problems, but the reasons for this were unclear. The first child died. After identification of mutations in the AChR pathway, the second child was started on an acetylcholine esterase inhibitor. Her ability to move improved greatly, her muscle weakness also improved, and she later began to walk. “This underlines the obvious therapeutic relevance of early clinical and genetic consideration of AChR pathway mutations”, says Dr. Hoffmann. “Doctors in pre and neonatal care should be aware of the importance of the AChR pathway in this group of diseases. Clinical examination and genetic testing can confirm the diagnosis and help to identify appropriate treatment.”

Scans of the genome of patients with schizophrenia have revealed rare spontaneous copy number mutations that account for at least 10 percent of the non-familial cases of the disease. Researchers describe specific genetic mutations present in individuals who have schizophrenia, but not present in their biological parents who do not have the disease. These individuals were eight times more likely to have these mutations than unaffected individuals. This new data, reported in the May 30 on-line issue of Nature Genetics, will help researchers account for the persistence of schizophrenia in the population despite low birth rates among people with the disease.Researchers at Columbia University Medical Center scanned the genome of 1,077 people which included 152 individuals with schizophrenia, 159 individuals without schizophrenia, and both of their biological parents for copy number mutations. They found mutations, either a gain or loss of genes, in 15 individuals diagnosed with schizophrenia that were not present in the chromosomes of either biological unaffected parent. Only two of such mutations were found in those without schizophrenia. Study subjects were from the European-origin Afrikaner population in South Africa, a genetically homogenous population that is ideal for genetic evaluation.

“We now know the cause of around 10 percent of the cases of sporadic schizophrenia,” said Maria Karayiorgou, M.D., professor of psychiatry, Columbia University Medical Center, the senior author on the study. “Schizophrenia is not as much of a ‘big black box’ as it used to be. The identification of these genes lets us know what brain development pathways are involved in disease onset, so that in the future we can look at better ways of treating this devastating disease.”

Schizophrenia affects approximately 1 percent of the population worldwide. About 40 percent of the disease is thought to be inherited, with the other 60 percent sporadically showing up in people whose family history does not include the disease.

One of the new or de novo mutations researchers found in more than one affected individual in this study was a deletion of a region of chromosome 22. Dr. Karayiorgou had previously provided evidence that loss of genes in this region, 22q11.2, was responsible for introducing “new” or sporadic cases of schizophrenia in the population. This confirms 22q11.2 as the only known recurrent such mutation linked to schizophrenia.

“We have already demonstrated 22q11.2 to be involved in sporadic schizophrenia and we have made considerable progress in understanding the underlying biological mechanisms,” said Dr. Gogos. “Now, we have a new set of mutations that we can investigate. The more information we have about the biological basis for this disease, the more information we can provide to those who suffer from it and their families.”

“Such abnormal deletions or duplications of genetic material are increasingly being implicated in schizophrenia and autism,” explains National Institute of Mental Health Director Thomas R. Insel, M.D. “Now we have a dramatic demonstration that genetic vulnerabilities for these illnesses may stem from both hereditary and non-hereditary processes. This line of research holds promise for improved treatments – and perhaps someday even prevention – of developmental brain disorders.”

Karayiorgou and co-senior author Joseph A. Gogos, M.D., Ph.D., associate professor of physiology and neuroscience at Columbia University Medical Center, agree that the goal is for psychiatrists to be able to inform patients that they have a mutation that is causing their disease and ultimately to be able to tailor treatments to individual patients based on their specific mutation. This tailored treatment is a ways off, according to Dr. Karayiorgou, but she says patients and their families are relieved to know that there is a biological cause of their illness.

The researchers plan to extend their screen for additional de novo mutations by using increased resolution scans to study additional families. They also plan to scrutinize further genes affected by the identified mutations through human genetics and animal model approaches.

A mat of nanowires with the touch and feel of paper could be an important new tool in the cleanup of oil and other organic pollutants, MIT researchers and colleagues report in the May 30 online issue of Nature Nanotechnology.The scientists say they have created a membrane that can absorb up to 20 times its weight in oil, and can be recycled many times for future use. The oil itself can also be recovered. Some 200,000 tons of oil have already been spilled at sea since the start of the decade.

“What we found is that we can make ‘paper’ from an interwoven mesh of nanowires that is able to selectively absorb hydrophobic liquids-oil-like liquids-from water,” said Francesco Stellacci, an associate professor in the Department of Materials Science and Engineering and leader of the work.

In addition to its environmental applications, the nanowire paper could also impact filtering and the purification of water, said Jing Kong, an assistant professor of electrical engineering in the Department of Electrical Engineering and Computer Science and one of Stellacci’s colleagues on the work. She noted that it could also be inexpensive to produce because the nanowires of which it is composed can be fabricated in larger quantities than other nanomaterials.

Stellacci explained that there are other materials that can absorb oils from water, “but their selectivity is not as high as ours.” In other words, conventional materials still absorb some water, making them less efficient at capturing the contaminant.

The new material appears to be completely impervious to water. “Our material can be left in water a month or two, and when you take it out it’s still dry,” Stellacci said. “But at the same time, if that water contains some hydrophobic contaminants, they will get absorbed.”

Made of potassium manganese oxide, the nanowires are stable at high temperatures. As a result, oil within a loaded membrane can be removed by heating above the boiling point of oil. The oil evaporates, and can be condensed back into a liquid. The membrane-and oil-can be used again.

Two key properties make the system work. First, the nanowires form a spaghetti-like mat with many tiny pores that make for good capillarity, or the ability to absorb liquids. Second, a water-repelling coating keeps water from penetrating into the membrane. Oil, however, isn’t affected, and seeps into the membrane.

The membrane is created by the same general technique as its low-tech cousin, paper. “We make a suspension of nanowires, like a suspension of cellulose [the key component of paper], dry it on a non-sticking plate, and we get pretty much the same results,” Stellacci said.

In a commentary accompanying the Nature Nanotechnology paper, Joerg Lahann of the University of Michigan concluded: “Stellacci and co-workers have provided an example of a nanomaterial that has been rationally designed to address a major environmental challenge.”

Blocking a common immune system response cleared up plaques associated with Alzheimer’s Disease and enabled treated mice to recover some lost memory, Yale University researchers report Friday in the journal Nature Medicine.Researchers hope the new approach may one day overcome one of the biggest obstacles to development of new dementia medications – the difficulty in finding drugs that can safely cross the blood-brain barrier.

The results of the research surprised the scientists working in the lab of Richard Flavell, senior author of the paper, chairman of the Department of Immunobiology at Yale and investigator with the Howard Hughes Medical Institute. Flavell’s team originally thought that blocking the immune system molecule TGF-β(or transforming growth factor), might actually increase the buildup of amyloid plaques associated with Alzheimer’s Disease

Earlier studies had shown that Alzheimer’s patients tend to have elevated amounts of TGF-β, which plays a key role in activating immune system response to injury. Some had thought the presence of the molecule was simply an attempt to quiet the inflammatory response caused by a buildup of plaque.

Instead, the team found that as much as 90 percent of the plaques were eliminated from the brains of mice genetically engineered to block TGF-β in the peripheral immune cells.

It was like a vacuum cleaner had removed the plaques,” Flavell said.

When the TGF-β pathway was interrupted in mice engineered to have Alzheimer’s, the mice showed an improved ability to perform some tests, including navigating mazes when compared to mice without TGF-β blocked. Scientists also found lower levels of other biological markers associated with the dementia.

When TGF-β was blocked, the immune system seemed to unleash immune cells known as peripheral macrophages. The macrophages passed through the blood-brain barrier and surrounded the neurons and plaques in the brains of mice. “If results from our study in mice engineered to develop Alzheimer’s-like dementia are supported by studies in humans, we may be able to develop a drug that could be introduced into the bloodstream to cause peripheral immune cells to target the amyloid plaques,” said Terrence Town, lead author of the study.

People with schizophrenia from families with no history of the illness were found to harbor eight times more spontaneous mutations – most in pathways affecting brain development – than healthy controls, in a study supported in part by the National Institutes of Health’s (NIH) National Institute of Mental Health (NIMH). By contrast, no spontaneous mutations were found in people with schizophrenia who had family histories of the illness.

“Our findings strongly suggest that rare, spontaneous mutations likely contribute to vulnerability in cases of schizophrenia from previously unaffected families,” said Maria Karayiorgou, M.D., of Columbia University, who led the research team. “This may also shed light on why the illness has frustrated efforts to implicate gene variants with major effects, and seems to defy natural selection by persisting in the population even though relatively few of those affected have children.”

Karayiorgou and her colleagues report on their whole genome study online in Nature Genetics, May 30, 2008.

“Such abnormal deletions or duplications of genetic material are increasingly being implicated in schizophrenia and autism,” explained NIMH Director Thomas R. Insel, M.D. “Now we have a dramatic demonstration that genetic vulnerabilities for these illnesses may not be inherited from parents, at least in the sense that these vulnerabilities were not present in the parental genome. This line of research holds promise for improved treatments – and perhaps someday even prevention – of developmental brain disorders.”

Although it’s known that genetics plays a major role in the transmission of both autism and schizophrenia, most cases are sporadic rather than familial.

Echoing findings of another recent study, Karayiorgou and her colleagues determined that most of the suspect mutations were not random, but found in genes and pathways involved in brain development. However, whether a mutation was spontaneous or inherited was not determined for most of the subjects included in the earlier study.

To pinpoint the sources of the glitches, the researchers in the new study compared genetic data from 369 subjects with data from their biological parents – in a total sample of 1,077 individuals drawn from the European ancestry Afrikaner population in South Africa. Including parental genes makes it possible to definitively determine what’s inherited.

Scans of each person’s genome detected the spontaneous mutations in 15 of 152 individuals (10 percent) with non-familial schizophrenia, and only in two of 159 people (1 percent) without the illness – the eight-fold difference. Such sporadic cases were only 1.5 times more likely than controls to harbor inherited mutations.

The researchers also found three deletions of genetic material at a site on chromosome 22 previously implicated in schizophrenia, confirming it as the only known recurrent such mutation linked to schizophrenia.

Nautiloids are the sole surviving family of externally-shelled cephalopods that thrived in the tropical oceans 450–150 million years ago. However, in the intervening years their modern soft bodied relatives dumped the shell and developed complex central nervous systems; which makes Nautilus ideally suited to discover the ‘evolutionary pathways that led to the development of the complex coleoid [soft bodied cephalopod] brains’ say Robyn Crook and Jennifer Basil. Knowing that the simple Nautilus brain lacks the structures required for memory in more sophisticated cephalopods, Crook and Basil decided to test the living fossil’s memory.

Training Nautilus pompilus to associate the smell of food with a blue light, the cephalopods eventually learned to respond to a flash of blue light by extending their tentacles. Then the scientists tested the cephalopods memories with a flash of light 3min, 30min, 1h, 6h, 12h and 24h after training. Amazingly, Nautilus remembered their training for up to an hour before the memory was lost, but then the memory returned 6h later, lasting up to 24h. Nautilus has both short and long term memory, just like modern cephalopods, despite lacking the same brain structures.

Crook and Basil are optimistic that the unsophisticated Nautilus brain could teach us how modern cephalopod brains evolved.

It’s stronger than steel and nylon, and more extensible than Kevlar. So what is this super-tough material? Spider silk; and learning how to spin it is one of the materials industries’ Holy Grails. John Gosline has been fascinated by spider silks and their remarkable toughness for most of his scientific career. He explains that if we’re to learn how to manufacture spider silk, we have to understand the relationship between the components and the spun fibre’s mechanical properties; which is why he is focusing on major ampullate silk, one of the many silks that spiders spin. According to Gosline, spiders use major ampullate silk for draglines and to build the frame and radial structures in webs, all of which have to deform and absorb enormous amounts of energy without fracturing. Comparing the amino acid sequences of major ampullate silk proteins from Araneus diadematus and Nephila clavipes, Gosline realised that the sequences differed on one count; Araneus silk is relatively rich in the amino acid proline, while proline levels in Nephila silk are very low. Curious to know how the presence of proline affects the silks, Gosline and his student, Ken Savage, set about comparing the silks’ mechanical properties to find out how the amino acid affects spider silk toughness.

However, obtaining consistent spider silk samples is a problem. Gosline explains that spiders adjust the way they manufacture their silks depending on their circumstances, so he and Savage left the spiders roaming free so that the strands of dragline silk that they dropped were as uniform as possible. Having established a reliable silk supply, Savage set about testing the silks’ mechanical properties. Gently stretching the dry silk while measuring the force on it, the team quickly realised that the silks behaved almost identically; the presence of proline had little or no effect on dry silk. However, when Savage began investigating the hydrated silk it was a completely different story. For a start, the wet Araneus silk shrank and swelled much more than the proline deficient Nephila silk. Savage also tested the silk’s stiffness, and found that the Nephila silk was almost ten times stiffer than the Araneus silk. Finally, knowing that regions of the silk proteins stack to form microscopic crystals in a fibre, Savage measured the fibre’s birefringence to see how the two silks compared and if the organisation of the proteins in the silk fibre changed when they were damp. The proteins in the Nephila silk were always more organised than the proteins in the Araneus silk, regardless of whether they were wet or dry. And as Savage stretched the silks, the degree of organisation in the hydrated Nephila silk increased much more than the Araneus silk.

Gosline realised that the different mechanical properties could be accounted for by the silk proteins’ amino acid composition. According to Gosline, proline amino acids are famed for breaking up the organised three-dimensional structures that protein chains fold into, so protein structures with high proline content would be poorly organised in comparison to proteins with little or no proline. Araneus silk contains 16% proline, found mostly in linker regions between the protein’s crystalline structures, which would make the linkers flexible and randomly arranged. Gosline realised that if this was the case, the hydrated silk might behave like an elastic band. Nephila silk, on the other hand, has a very low proline content in the linker regions, allowing the linkers to form a relatively well organised crystalline structure and behave more like a stiff spring. Gosline and Savage decided to investigate both silks’ stretchiness to see if they were more rubber-like or spring-like.

Stretching samples of the hydrated silks, Savage gently raised and lowered the temperature from 30 to 10°C while carefully measuring the minute forces required to maintain the extension. For Nephila silk the force remained essentially constant as the temperature changed, a clear indication of spring-like elasticity. However, for the proline-rich Araneus silk the force varied in direct proportion to the temperature, behaving like a rubber-band. So proline-rich spider silks extend like floppy rubber bands, while spider silks with low proline levels behave more like rigid springs.

Having found that proline amino acids have a dramatic effect on the mechanical behaviour of hydrated spider silks, Gosline and Savage are keen to find out why the behaviour of the dry silks is almost indistinguishable and what the functional significance is of the different proline contents.

The investigational chemotherapeutic agent eribulin mesylate (E7389) demonstrated activity in a heavily pretreated population of women with locally advanced or metastatic breast cancer, according to results of a multi-center Phase II clinical trial. The study also suggests that eribulin mesylate has a manageable tolerability profile, with a low incidence of Grade 3 (severe) and no Grade 4 (disabling or life-threatening) neuropathy. These data (abstract #1084) will be presented at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) on Monday, June 2 from 2 to 6 p.m. at S Hall A1 of McCormick Place.¡°The anti-tumor activity of eribulin mesylate, as observed in this study, is encouraging, given the limited treatment options for women with advanced breast cancer who have previously received multiple lines of therapy,¡± said lead investigator Linda T. Vahdat, MD, of Weill Cornell Medical College in New York. ¡°The subjects in this trial had received a median of four prior chemotherapy regimens that included an anthracycline, a taxane and capecitabine.¡±

About Study 211 Study 211 is a Phase II, open-label, single-arm study evaluating the efficacy and safety of eribulin mesylate in patients with locally advanced or metastatic breast cancer who had received an anthracycline, a taxane and capecitabine as prior therapy, and who were refractory to their last chemotherapy regimen, as documented by progression on or within six months of that therapy.

Of 299 patients enrolled in the study, 291 were treated with eribulin mesylate. The median age of those patients was 56 years (range: 26-80 years). Eribulin mesylate was administered at a dose of 1.4mg/m2 as a 2- to 5-minute intravenous infusion on Days 1 and 8 of a 21-day cycle. Patients received a median of four cycles of eribulin mesylate (range 1-27). No premedication to prevent hypersensitivity was required.

Two-hundred sixty-nine patients met the key inclusion criteria. In patients who received a median of four cycles of eribulin mesylate, Overall Response Rate (ORR) by Independent Review (IR) was 9.3% (all Partial Responses (PR); 95% confidence interval [CI]: 6.1%-13.4%). Investigator-assessed ORR was 14.1% (1 CR; 95% CI: 10.2%-18.9%). Nearly half (46.5%) the patients had stable disease (SD) after treatment with eribulin mesylate. The clinical benefit rate (CBR, defined as CR+PR+SD ¡Ý6 months) was 17.1% (95% CI: 12.8%-22.1%).

The median duration of response was 4.2 months (126 days, range: 42 -258 days; 95% CI: 86-147). Median progression-free survival (PFS) was 2.6 months (79 days, range: 1*-397 days), and the median overall survival (OS) rate was 10.3 months (315 days, range: 19-604 days; 95% CI: 279-350). The six-month PFS and OS rates were 16.0% (95% CI: 8.6-17.0) and 72.3%, respectively (95% CI: 66.9-77.6).

The safety analysis included all 291 patients who received treatment with eribulin mesylate. Patients with up to Grade 2 peripheral neuropathy were included in the study. The most frequently reported Grade 3 (severe) or Grade 4 (disabling or life- threatening) adverse events were neutropenia (a decrease in the number of granular white blood cells, 54%); febrile neutropenia, 5.5%, leukopenia (low white blood cell count, 14%), and weakness/fatigue (10%; no Grade 4 events). Grade 3 peripheral neuropathy (a functional disturbance or damage to nerves outside the brain and spinal cord) was reported in 5.5% of patients. No Grade 4 peripheral neuropathy events were reported. No correlation was seen between Grade 2 peripheral neuropathy and deterioration.

“In this study, eribulin mesylate appeared to have an acceptable tolerability profile, particularly with regard to the low incidence of peripheral neuropathy,” noted Vahdat. “None of the reported cases of neuropathy were disabling, suggesting that eribulin mesylate, if approved, may be a useful addition to the treatment armamentarium for advanced breast cancer.”