Tuesday, February 15, 2011

What a ride! Researchers take molecules for a spin

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"This is no cartoon. It's a real molecule, with all the interactions taking place correctly," said Anatoly Kolomeisky as he showed an animation of atoms twisting and turning about a central hub like a carnival ride gone mad.

Kolomeisky, a Rice University associate professor of chemistry, was offering a peek into a molecular midway where atoms dip, dive and soar according to a set of rules he is determined to decode.

Kolomeisky and Rice graduate student Alexey Akimov have taken a large step toward defining the behavior of these molecular whirligigs with a new paper in the American Chemical Society's Journal of Physical Chemistry C. Through molecular dynamics simulations, they defined the ground rules for the rotor motion of molecules attached to a gold surface.

It's an extension of their work on Rice's famed nanocars, developed primarily in the lab of James Tour, Rice's T.T. and W.F. Chao Chair in Chemistry as well as a professor of mechanical engineering and materials science and of computer science, but for which Kolomeisky has also constructed molecular models.

Striking out in a different direction, the team has decoded several key characteristics of these tiny rotors, which could harbor clues to the ways in which molecular motors in human bodies work.

The motion they described is found everywhere in nature, Kolomeisky said. The most visible example is in the flagella of bacteria, which use a simple rotor motion to move. "When the flagella turn clockwise, the bacteria move forward. When they turn counterclockwise, they tumble." On an even smaller level, ATP-synthase, which is an enzyme important to the transfer of energy in the cells of all living things, exhibits similar rotor behavior -- a Nobel Prize-winning discovery.

Understanding how to build and control molecular rotors, especially in multiples, could lead to some interesting new materials in the continuing development of machines able to work at the nanoscale, he said. Kolomeisky foresees, for instance, radio filters that would let only a very finely tuned signal pass, depending on the nanorotors' frequency.

"It would be an extremely important, though expensive, material to make," he said. "But if I can create hundreds of rotors that move simultaneously under my control, I will be very happy."

The professor and his student cut the number of parameters in their computer simulation to a subset of those that most interested them, Kolomeisky said. The basic-model molecule had a sulfur atom in the middle, tightly bound to a pair of alkyl chains, like wings, that were able to spin freely when heated. The sulfur anchored the molecule to the gold surface.

While working on a previous paper with researchers at Tufts University, Kolomeisky and Akimov saw photographic evidence of rotor motion by scanning tunneling microscope images of sulfur/alkyl molecules heated on a gold surface. As the heat rose, the image went from linear to rectangular to hexagonal, indicating motion. What the pictures didn't indicate was why.

That's where computer modeling was invaluable, both on the Kolomeisky lab's own systems and through Rice's SUG@R platform, a shared supercomputer cluster. By testing various theoretical configurations -- some with two symmetrical chains, some asymmetrical, some with only one chain -- they were able to determine a set of interlocking characteristics that control the behavior of single-molecule rotors.

First, he said, the symmetry and structure of the gold surface material (of which several types were tested) has a lot of influence on a rotor's ability to overcome the energy barrier that keeps it from spinning all the time. When both arms are close to surface molecules (which repel), the barrier is large. But if one arm is over a space -- or hollow -- between gold atoms, the barrier is significantly smaller.

Second, symmetric rotors spin faster than asymmetric ones. The longer chain in an asymmetric pair takes more energy to get moving, and this causes an imbalance. In symmetric rotors, the chains, like rigid wings, compensate for each other as one wing dips into a hollow while the other rises over a surface molecule.

Third, Kolomeisky said, the nature of the chemical bond between the anchor and the chains determines the rotor's freedom to spin.

Finally, the chemical nature of rotating groups is also an important factor.

Kolomeisky said the research opens a path for simulating more complex rotor molecules. The chains in ATP-synthase are far too large for a simulation to wrangle, "but as computers get more powerful and our methods improve, we may someday be able to analyze such long molecules," he said.

Rice University

Level of tumor protein indicates chances cancer will spread

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Researchers at the National Institutes of Health and the University of Hong Kong have discovered that high levels of a particular protein in cancer cells are a reliable indicator that a cancer will spread.

By measuring the protein’s genetic material in tumors that had been surgically removed from patients, along with measuring the genetic material from surrounding tissue, the researchers could predict at least 90 percent of the time whether a cancer would spread within two years.

The findings raise the long term possibilities of new tests to gauge the likelihood that a cancer will spread and, ultimately, of a treatment that could prevent cancer from spreading.

The protein, known as CPE-delta N, is a form of carboxypeptidase E (CPE). Ordinarily, CPE is involved in processing insulin and other hormones. CPE-delta N, a variant of CPE, was present in high amounts in tumors that had spread and, to a much lesser degree, in surrounding tissues.

Cancer cells can break away from a primary tumor and spread, or metastasize, to other parts of the body, where they form new tumors. Metastatic cancer is often fatal, and health care practitioners seek to contain cancer early, before it can metastasize.

"Testing for CPE-delta N, if combined with existing diagnostic methods, offers the possibility of more accurately estimating the chances that a cancer will spread," said Alan E. Guttmacher, M.D., director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, which supported the study. "Conceivably, a patient’s CPE-delta N levels could be a key guide in individualizing their cancer care to improve outcome."

The researchers estimated the likelihood of metastasis in tumor samples and tissues from patients with liver cancer (http://www.cancer.gov/cancertopics/types/liver/) and two rare tumors, pheochromocytoma and paraganglioma (http://www.cancer.gov/cancertopics/types/pheochromocytoma/). They found that tumor samples from patients whose cancers had later metastasized had elevated levels of CPE-delta N.

Tests indicating high levels of the protein predicted the spread of a cancerous tumor even when conventional staging — diagnostic techniques to gauge the extent and seriousness of a cancer — indicated that spread was unlikely. The finding raises the possibility that testing for CPE-delta N might be used in combination with conventional staging to further refine treatment. For example, if conventional staging indicated that a cancer was unlikely to spread, but a patient's tumor had high CPE-delta N levels, that patient might be referred for more intensive therapies normally reserved for higher stage cancers.

The study's senior authors were Y. Peng Loh of NICHD's Section on Cellular Neurobiology and Ronnie Poon from the University of Hong Kong. Other authors were from the NICHD, University of Hong Kong, the Lawson Health Research Institute in Ontario, Canada; the NIH’s National Cancer Institute (NCI); and the Warren Grant Magnuson Clinical Center at NIH. The research was supported in part by NICHD, NCI, The University of Hong Kong and by the Canadian government.

The findings appear in the Journal of Clinical Investigation.

The researchers tested for CPE-delta N indirectly, by measuring levels of a molecule that assists in manufacturing the protein. RNA (ribonucleic acid) works with the information in a gene to make a particular protein — in this case, CPE-delta N.

In an analysis of tissue from 99 patients with liver cancer, the researchers compared the amount of CPE-delta N RNA from the patients’ tumors with the RNA levels in surrounding tissue.

The researchers found that when the level of CPE delta-N RNA in tumors was more than twice that in the surrounding tissue, the cancer was highly likely to return or to metastasize within two years. At or below this threshold level, the cancer was much less likely to recur. Using this threshold measure, the researchers accurately predicted metastasis or recurrence in more than 90 percent of cases. Conversely, their predictions that tumors would not return in the two-year period were accurate 76 percent of the time.

Next, the researchers measured CPE-delta N RNA levels from stored tumor tissue originally removed from 14 patients with pheochromocytoma, a rare tumor of the adrenal glands, and paraganglioma, a rare tumor primarily occurring in the adrenals but sometimes in other parts of the body. Because the adrenal glands are very small, tissue surrounding the tumor was not obtainable, so the researchers measured the amount of CPE-delta N RNA in the tumor tissue only. The number of copies ranged from 150,000 to 15 million per 200 micrograms of tissue. In all of the cases where cancer was found to have recurred or metastasized, CPE-delta N RNA levels were greater than 1 million. The researchers found no metastasis or recurrence in cases in which tumors had less than 250,000 copies. Patients' status was tracked for up to eight years.

In addition, the researchers examined cells from liver, breast, colon, and head and neck, tumors and found that those known to spread most aggressively had the highest levels of CPE-delta N RNA.

The researchers next tested a potential strategy for preventing the spread of cancer by halting the production of CPE-delta N in two different mouse models. The strategy involved treating metastatic tumors with antisense RNA, which binds to RNA, preventing it from making a protein.

In the first experimental model, the researchers transplanted highly metastatic liver cancer cells beneath the skin of mice. Half the transplants were first treated with antisense RNA specific for CPE-delta N, the other half were not. After 30 days, the tumors in the mice not treated with antisense RNA for CPE-delta N were much larger than the treated tumors in the remaining mice. Next, the researchers removed the tumors from the first set of mice and transplanted them into the livers of a second group of mice. After 35 days, only the untreated tumors had spread and formed new tumors.

Dr. Loh explained that the method used in the study might some day be used to treat cancers in human beings. Currently, there are no means to deliver the antisense RNA to tumor cells. A potential approach might involve modifying a virus to carry the antisense RNA into cells.

Similarly, further research might lead to the development of drugs or other measures to block CPE-delta N and so prevent cancer from spreading.

(Photo: NIH)

National Institutes of Health

Sharing Child Caregiving May Increase Parental Conflict, Study Finds

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Parents who share caregiving for their preschool children may experience more conflict than those in which the mother is the primary caregiver, according to a new study.

Results showed that couples had a stronger, more supportive co-parenting relationship when the father spent more time playing with their child. But when the father participated more in caregiving, like preparing meals for the child or giving baths, the couples were more likely to display less supportive and more undermining co-parenting behavior toward each other.
Sarah Schoppe-Sullivan

The results were surprising, and may be disappointing for people who believe mothers and fathers should share equally in the caregiving for their children, said Sarah Schoppe-Sullivan, co-author of the study and associate professor of human development and family science at Ohio State University.

But, she said, it shows that there is not just one way to share parenting duties.

“I don’t think this means that for every family, a father being involved in caregiving is a bad thing. But it is not the recipe for all couples,” Schoppe-Sullivan said.

“You can certainly have a solid co-parenting relationship without sharing caregiving responsibilities equally.”

Schoppe-Sullivan conducted the study with Rongfang Jia, a graduate student at Ohio State. The study appears in the January 2011 issue of the journal Developmental Psychology.

The study was designed to test how a father’s involvement in child caregiving affected the couple’s co-parenting relationship -- how parents interact together while parenting their child.

The study began with 112 Midwestern couples, most of whom were married, who had a 4-year-old child. At the beginning of the study, fathers and mothers filled out questionnaires that asked how often they were involved in play activities with their children (such as giving them rides on their shoulders and backs) and how often they were involved in caregiving activities (such as giving the child a bath.)

The researchers then observed the couple for 20 minutes while they assisted their child in completing two tasks: drawing a picture of their family together and building a house out of a toy building set.

These tasks are a bit difficult for preschoolers and required the guidance of both parents, which gave the researchers the opportunity to detect how much the parents supported each other or undermined each other in their co-parenting, Schoppe-Sullivan said.

The researchers looked for signs of supportive co-parenting, such as couples encouraging and cooperating with each other as they helped their child. Researchers also looked for evidence of couples criticizing each other’s parenting or trying to “outdo” each other in their efforts to work with the child.

One year later, the couples returned to the laboratory and participated in a similar observed activity with their child.

The results showed that, in general, when fathers indicated they played more with their child at the beginning of the study, the couple showed more supportive co-parenting one year later. However, when fathers said they participated more in caregiving, the couples showed lower levels of supportive co-parenting one year later.

The gender of the children seemed to play a role, Schoppe-Sullivan said. Fathers playing with sons reduced undermining behavior more than did fathers playing with daughters.

“Having fathers involved in play activity is good for co-parenting, but might be especially good for boys,” she said. “But, fathers are more likely to get into conflicts with mothers when they are heavily involved in caregiving of boys.”

The findings in the study held true even when the researchers compared dual and single-income families, and when they took into account a wide variety of other demographic factors that may have affected the results, such as fathers’ education and work hours, family income, family size and the length of the couple’s relationship.

She noted that this study only included children as they moved from 4 to 5 years old. How father involvement relates to co-parenting may be different with younger or older children.

The results of this study fit into other work by Schoppe-Sullivan that found mothers can act as “gatekeepers,” either fostering or curtailing how much fathers are involved in caring for their children.

Even though fathers’ involvement in child rearing has increased over the last few decades, mothers still do more child care, even when they work full-time, she said. Many mothers still feel they are in charge of child care.

“There might be some ambivalence on the part of mothers in allowing fathers to participate in day-to-day child care,” she said. “But fathers might be ambivalent too, and may not be happy about shouldering more of the caregiving. That may contribute to less supportive co-parenting.”

Even if both parents want the father to contribute more, it can be difficult to share responsibilities without some disagreements.

“If the mother is solely responsible for child care, she gets to determine how it is done. But if she is sharing those duties with the father, there is more opportunity for conflict about how tasks should be done,” she said.

Overall, Schoppe-Sullivan said the results show that each couple has to decide for themselves which way works best when it comes to taking care of their children.

“There is more than one path to an effective co-parenting relationship,” she said.

“Effective co-parenting is not necessarily synonymous with equally sharing caregiving duties.”

(Photo: OSU)

Ohio State University

Neurobiologists find that weak electrical fields in the brain help neurons fire together

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The brain—awake and sleeping—is awash in electrical activity, and not just from the individual pings of single neurons communicating with each other. In fact, the brain is enveloped in countless overlapping electric fields, generated by the neural circuits of scores of communicating neurons. The fields were once thought to be an "epiphenomenon, a 'bug' of sorts, occurring during neural communication," says neuroscientist Costas Anastassiou, a postdoctoral scholar in biology at the California Institute of Technology (Caltech).

New work by Anastassiou and his colleagues, however, suggests that the fields do much more—and that they may, in fact, represent an additional form of neural communication.

"In other words," says Anastassiou, the lead author of a paper about the work appearing in the journal Nature Neuroscience, "while active neurons give rise to extracellular fields, the same fields feed back to the neurons and alter their behavior," even though the neurons are not physically connected—a phenomenon known as ephaptic coupling. "So far, neural communication has been thought to occur at localized machines, termed synapses. Our work suggests an additional means of neural communication through the extracellular space independent of synapses."

Extracellular electric fields exist throughout the living brain, though they are particularly strong and robustly repetitive in specific brain regions such as the hippocampus, which is involved in memory formation, and the neocortex, the area where long-term memories are held. "The perpetual fluctuations of these extracellular fields are the hallmark of the living and behaving brain in all organisms, and their absence is a strong indicator of a deeply comatose, or even dead, brain," Anastassiou explains.

Previously, neurobiologists assumed that the fields were capable of affecting—and even controlling—neural activity only during severe pathological conditions such as epileptic seizures, which induce very strong fields. Few studies, however, had actually assessed the impact of far weaker—but very common—non-epileptic fields. "The reason is simple," Anastassiou says. "It is very hard to conduct an in vivo experiment in the absence of extracellular fields," to observe what changes when the fields are not around.

To tease out those effects, Anastassiou and his colleagues, including Caltech neuroscientist Christof Koch, the Lois and Victor Troendle Professor of Cognitive and Behavioral Biology and professor of computation and neural systems, focused on strong but slowly oscillating fields, called local field potentials (LFP), that arise from neural circuits composed of just a few rat brain cells. Measuring those fields and their effects required positioning a cluster of tiny electrodes within a volume equivalent to that of a single cell body—and at distances of less than 50 millionths of a meter from one another.

"Because it had been so hard to position that many electrodes within such a small volume of brain tissue, the findings of our research are truly novel," Anastassiou says. Previously, he explains, "nobody had been able to attain this level of spatial and temporal resolution."

An "unexpected and surprising finding was how already very weak extracellular fields can alter neural activity," he says. "For example, we observed that fields as weak as one millivolt per millimeter robustly alter the firing of individual neurons, and increase the so-called "spike-field coherence"—the synchronicity with which neurons fire with relationship to the field."In the mammalian brain, we know that extracellular fields may easily exceed two to three millivolts per millimeter. Our findings suggest that under such conditions, this effect becomes significant."

What does that mean for brain computation? "Neuroscientists have long speculated about this," Anastassiou says. "Increased spike-field coherency may substantially enhance the amount of information transmitted between neurons as well as increase its reliability. Moreover, it has been long known that brain activity patterns related to memory and navigation give rise to a robust LFP and enhanced spike-field coherency. We believe ephaptic coupling does not have one major effect, but instead contributes on many levels during intense brain processing."

Can external electric fields have similar effects on the brain? "This is an interesting question," Anastassiou says. "Indeed, physics dictates that any external field will impact the neural membrane. Importantly, though, the effect of externally imposed fields will also depend on the brain state. One could think of the brain as a distributed computer—not all brain areas show the same level of activation at all times.

"Whether an externally imposed field will impact the brain also depends on which brain area is targeted. During epileptic seizures, pathological fields can be as strong as 100 millivolts per millimeter¬—such fields strongly entrain neural firing and give rise to super-synchronized states." And that, he adds, suggests that electric field activity—even from external fields—in certain brain areas, during specific brain states, may have strong cognitive and behavioral effects.

Ultimately, Anastassiou, Koch, and their colleagues would like to test whether ephaptic coupling affects human cognitive processing, and under which circumstances. "I firmly believe that understanding the origin and functionality of endogenous brain fields will lead to several revelations regarding information processing at the circuit level, which, in my opinion, is the level at which percepts and concepts arise," Anastassiou says. "This, in turn, will lead us to address how biophysics gives rise to cognition in a mechanistic manner—and that, I think, is the holy grail of neuroscience."

(Photo: Figure 4 in Anastassiou et., Nature Neuroscience, 2011)

California Institute of Technology (Caltech)

Lampreys give clues to evolution of immune system

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Biologists have discovered that primitive, predatory lampreys have structures within their gills that play the same role as the thymus, the organ where immune cells called T cells develop in mammals, birds and fish.

The finding suggests that in vertebrate evolution, having two separate organs for immune cell development -- the bone marrow for B cells and the thymus for T cells -- may have preceded the appearance of the particular features that mark those cells, such as antibodies and T cell receptors.

The results were published Feb. 3 by the journal Nature.

The first author of the paper is postdoctoral fellow Baubak Bajoghli at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany. The co-senior authors are Thomas Boehm, MD, group leader at the Max Planck Institute, and Max Cooper, MD, professor of pathology and laboratory medicine at Emory University School of Medicine and the Emory Vaccine Center, and a Georgia Research Alliance Eminent Scholar.

"Our research has allowed us to see that lampreys have cells that resemble our T cells and B cells, but until recently, we didn't know where they developed or much about how," says Cooper, who made pioneering studies of the "two-arm" nature of the immune system, including defining the role of the thymus, at the University of Minnesota in the 1960s.

"We can now assume that the lamprey has a dual immune defense system similar to that of humans," says Boehm.

For commercial and recreational fishermen, lampreys represent a threat. For biologists, lampreys represent an opportunity to envision the evolutionary past, because of their status as "living fossils" that haven't changed in millions of years. Lampreys are thought to be an early offshoot on the evolutionary tree, before sharks and fish. Their lack of jaws distinguishes them from sharks or other types of fish.

Despite their primitive nature, lampreys do have a surprisingly sophisticated immune system. Blood cells develop in lampreys' typhlosole, an organ that lies next to the intestine. Lampreys have proteins in their blood that grab on to invaders like our antibodies, but structurally, those proteins don't look like antibodies.

Mammals, birds and fish have two types of immune cells, which each develop in separate places. B cells, which produce antibodies, develop in the bone marrow and fetal liver, while T cells, which recognize their targets by cell-to-cell contact, develop in the thymus. In humans, the thymus is located in the upper chest, under the throat.

The vertebrate thymus is a place where developing T cells must "sink or swim," because immature T cells must rearrange certain genes as part of their development. Most of the cells die because the rearrangement process is imprecise, and cells with improperly rearranged genes are screened out. The Emory/Max Planck team discovered that this same type of screening of non-functional genes appears to be occurring in the lamprey "thymoids" located in the tips of the gill filament.

"We don't know much about how this process is happening, but we were able to show that functional copies are found in the blood, while non-functional copies are only found in the thymoid," Cooper says.

In addition, in cells lining both the vertebrate thymus and lamprey thymoid, a gene is turned on (FOXN1) that is essential for thymus development in mice and humans, the scientists found. Mice that have this gene mutated lack a thymus and are called "nude" mice because they have no hair.

"Taken together, the results suggest that this basic feature of the immune system, where two types of cells develop in separate places, may have evolved before jawed and jawless vertebrates split onto different paths," Cooper says. "Having two companion arms of the immune system may be important so that the two arms can regulate each other and prevent autoimmunity."

Emory University

An extra 5 years of life an unexpected benefit of osteoporosis treatment

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Australian clinical researchers have noted an extraordinary and unexpected benefit of osteoporosis treatment – that people taking bisphosphonates are not only surviving well, better than people without osteoporosis, they appear to be gaining an extra five years of life. These findings are published in the Journal of Clinical Endocrinology and Metabolism, now online.

Associate Professor Jacqueline Center and Professor John Eisman, from Sydney's Garvan Institute of Medical Research, based their findings on data from the long running Dubbo Osteoporosis Epidemiology Study.

Out of a total cohort of around 2,000, a sub-group of 121 people were treated with bisphosphonates for an average of 3 years. When compared with other sub-groups taking other forms of treatment, such as Vitamin D (with or without calcium) or hormone therapy, the longer life associated with bisphosphonate treatment was marked and clear.

"While the results seemed surprisingly good, they are borne out by the data – within the limitations of any study – and appear to apply to men as well as women," said Associate Professor Center. "When we first looked at the figures, we thought that there had to be a fallacy, that we were missing something. One of the most obvious things might be that these are people who seek medical attention, so may be healthier and live longer. So we compared the bisphosphonate group with people taking Vitamin D and calcium or women on hormone therapy."

"The comparison against these other groups of similarly health-aware people simply confirmed that our results were not skewed by that factor." Center continued. "In a group of women with osteoporotic fractures over the age of 75, you would expect 50 percent to die over a period of five years. Among women in that age group who took bisphosphonates, the death rate dropped to 10 percent. Similarly, in a group of younger women, where you would expect 20-25 percent to die over five years, there were no deaths. The data were consistent with about a five year survival advantage for people on bisphosphonates."

"We speculate that it may have something to do with the fact that bone acts as a repository for toxic heavy metals such as lead and cadmium," said Professor Eisman. "So when people get older, they lose bone. When this happens, these toxic materials are released back into the body and may adversely affect health. By preventing bone loss, bisphosphonates prevent some of this toxic metal release. While we know that this is the case, we don't yet have evidence that this produces the survival benefit."

"Osteoporosis is a big societal burden and remains a poorly understood and severely undertreated disease in Australia," said Eisman. "Only about 30 percent of women and 10 percent of men with osteoporosis receive treatment, which is unacceptable when you consider that people could be helped, and death could be delayed by several years. There is good evidence – even without this study - that treating osteoporosis reduces fractures and reduces mortality."

The Endocrine Society


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Triceratops and Torosaurus have long been considered the kings of the horned dinosaurs. But a new discovery traces the giants' family tree further back in time, when a newly discovered species appears to have reigned long before its more well-known descendants, making it the earliest known member of its family.

The new species, called Titanoceratops after the Greek myth of the Titans, rivaled Triceratops in size, with an estimated weight of nearly 15,000 pounds and a massive eight-foot-long skull.

Titanoceratops, which lived in the American southwest during the late Cretaceous period around 74 million years ago, is the earliest known triceratopsin, suggesting the group evolved its large size more than five million years earlier than previously thought, according to Nicholas Longrich, the paleontologist at Yale who made the discovery. The finding, which will appear in an upcoming issue of the journal Cretaceous Research, helps shed light on the poorly understood origins of these giant horned dinosaurs.

Longrich was searching through scientific papers when he came across a description of a partial skeleton of a dinosaur discovered in New Mexico in 1941. The skeleton went untouched until 1995, when it was finally prepared and identified incorrectly as Pentaceratops, a species common to the area. When the missing part of its frill — the signature feature of the horned dinosaurs — was reconstructed for display in the Oklahoma Museum of Natural History, it was modeled after Pentaceratops.

"When I looked at the skeleton more closely, I realized it was just too different from the other known Pentaceratops to be a member of the species," Longrich said, adding that the specimen's size indicated that it likely weighed about twice as much as adult Pentaceratops. The new species is very similar to Triceratops, but with a thinner frill, longer nose and slightly bigger horns, Longrich said.

Instead, Longrich believes that Titanoceratops is the ancestor of both Triceratops and Torosaurus, and that the latter two split several millions years after Titanoceratops evolved. "This skeleton is exactly what you would expect their ancestor to look like," he said.

Titanoceratops was probably only around for about a million years, according to Longrich, while the triceratopsian family existed for a total of about 10 million years and roamed beyond the American southwest into other parts of the country and as far north as Canada.

In order to confirm the discovery beyond any trace of a doubt, Longrich hopes paleontologists will find other fossil skeletons that include intact frills, which would help confirm the differences between Titanoceratops and Pentaceratops.

"There have got to be more of them out there," Longrich said.

(Photo: Yale U.)

Yale University


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A team of Yale University scientists has synthesized for the first time a chemical compound called lomaiviticin aglycon, leading to the development of a new class of molecules that appear to target and destroy cancer stem cells.

Chemists worldwide have been interested in lomaiviticin's potential anticancer properties since its discovery in 2001. But so far, they have been unable to obtain significant quantities of the compound, which is produced by a rare marine bacterium that cannot be easily coaxed into creating the molecule. For the past decade, different groups around the world have been trying instead to synthesize the natural compound in the lab, but without success.

Now a team at Yale, led by chemist Seth Herzon, has managed to create lomaiviticin aglycon for the first time, opening up new avenues of exploration into novel chemotherapies that could target cancer stem cells, thought to be the precursors to tumors in a number of different cancers including ovarian, brain, lung, prostate and leukemia. Their discovery appears online today in the Journal of the American Chemical Society.

"About three quarters of anticancer agents are derived from natural products, so there's been lots of work in this area," Herzon said. "But this compound is structurally very different from other natural products, which made it extremely difficult to synthesize in the lab."

In addition to lomaiviticin aglycon, Herzon's team also created smaller, similar molecules that have proven extremely effective in killing ovarian stem cells, said Gil Mor, M.D., a researcher at the Yale School of Medicine and Yale Cancer Center who is collaborating with Herzon to test the new class of molecules' potential as a cancer therapeutic.

The scientists are particularly excited about lomaiviticin aglycon's potential to kill ovarian cancer stem cells because the disease is notoriously resistant to Taxol and Carboplatin, two of the most common chemotherapy drugs. "Ovarian cancer has a high rate of recurrence, and after using chemotherapy to fight the tumor the first time, you're left with resistant tumor cells that tend to keep coming back," Mor explained. "If you can kill the stem cells before they have the chance to form a tumor, the patient will have a much better chance of survival — and there aren't many potential therapies out there that target cancer stem cells right now."

Herzon's team, which managed to synthesize the molecule in just 11 steps starting from basic chemical building blocks, has been working on the problem since 2008 and spent more than a year on just one step of the process involving the creation of a carbon-carbon bond. It was an achievement that many researchers deemed impossible, but while others tried to work around having to create that bond by using other techniques, the team's persistence paid off.

"A lot of blood, sweat and tears went into creating that bond," Herzon said. "After that, the rest of the process was relatively easy."

Next, the team will continue to analyze the compound to better understand what's happening to the stem cells at the molecular level. The team hopes to begin testing the compounds in animals shortly.

"This is a great example of the synergy between basic chemistry and the applied sciences," Herzon said. "Our original goal of synthesizing this natural product has led us into entirely new directions that could have broad impacts in human medicine."

(Photo: Yale U.)

Yale University


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Nacre, commonly known as mother-of-pearl, is the iridescent material lining many mollusk shells. It is part of a two-layer armor system that protects the animal from predators. The brittle outer layer of the shell absorbs the initial impact, but is prone to cracking. To prevent these cracks from catastrophically propagating through the shell to the animal itself, the nacreous layer is surprisingly strong and tough, with outstanding crack arresting properties. Thus it acts as a lining to maintain the integrity of the shell in the event of cracking of the outer layer.

"What makes this natural material unique is that it is composed of relatively weak constituents," said Owen Loh, a graduate student at Northwestern University. At the microscale, brittle calcite tablets are stacked in a brick-and-mortar-like structure with thin layers of biopolymer lining the interfaces between tablets. This results in a material that well outperforms its individual constituents. For example, the toughness of nacre is orders of magnitude greater than that of the tablet material itself. In addition, nacre is at once strong and tough, a combination that is generally mutually exclusive in engineering materials.

As a result, nacre has been the object of significant interest within the materials community and serves as a model after which numerous man-made composite materials are designed. This includes composites for light-weight armor systems and structural elements in transportation and aerospace applications.

Nacre's outstanding performance has long been attributed to its brick-and-mortar microstructure. However, the specific attributes of this hierarchical structure, which contribute to the toughness of nacre, have been the subject of debate. As a result, efforts to translate deformation mechanisms observed in nacre into man-made composite materials have been widespread but mostly unsuccessful.

In a paper published online in the journal Nature Communications, Horacio Espinosa, the James N. and Nancy J. Farley Professor in Manufacturing and Entrepreneurship at the McCormick School of Engineering and Applied Science at Northwestern, Loh and colleagues report the identification of specific characteristics of the material microstructure that enable its outstanding performance. By performing detailed fracture experiments within an atomic force microscope, the group was able to directly visualize and quantify the way the tablets slid relative to each other as the material is deformed.

The group previously found that the tablets are not perfectly flat but instead have an inherent waviness in their surfaces. As a result, they tend to interlock as they slide relative to each other, spreading damage and dissipating energy over large areas. "We published these results before but it took atomic scales experiments to confirm our hypothesis on the origin of toughness in these biomaterials," Espinosa said.

The group then applied the findings to the design of artificial composites. "We took what we learned from natural nacre and designed a scaled-up artificial composite material with an interlocking tablet structure," said Pablo Zavattieri, a co-author of the paper and assistant professor of civil engineering at Purdue University. "By applying nacre's highly effective toughening mechanism to this material, we were able to achieve a remarkable improvement in energy dissipation."

The findings have important implications for future design of high-performance composite materials. "We believe these findings may hold a key to realizing the outstanding potential of nanocomposites," Espinosa said. "While carbon nanotubes and other nanoscale reinforcements utilized in these materials have unprecedented properties, their performance has yet to be translated to bulk composites. By implementing toughening mechanisms such as those we found in natural nacre, we may be able to achieve this."

(Photo: Northwestern U.)

Northwestern University


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Laser welding is on the advance, but it also has its limits: it has been impossible to fuse two transparent plastic components together – up until now. Researchers have now succeeded in circumventing this hurdle – by choosing the right wavelength. The new welding process is revolutionizing bioanalytics.

It’s a quick process, generates almost no waste and is extremely precise: within a few seconds, a laser beam has welded the casing and speedometer cover together – without any screws, clamps or glues whatsoever. The result is a perfect weld seam scarcely visible to the naked eye. There are no sparks or particles flying through the air during welding. What’s more: the resulting heat is confined to a minimal area. This protects the material. Many industries have now turned to welding plastics with a laser.

Still, the technology has its limits; when it comes to fusing two plastic components together, for instance, there is little freedom of choice. Up until now, the upper joining part had to be transparent to permit the laser to shine through unimpeded while the lower joining part absorbed the radiation. This usually meant soot particles had to be blended into the plastic. These particles absorb the energy of the laser beam and transmit the fusion heat generated to the upper joining part. “Up until now, you usually had to choose a single plastic combination: transparent and black. There are lots of applications – in medical technology, for instance – where what’s needed is a combination of two transparent plastics,” explains Dr.-Ing. Alexander Olowinsky, project manager at the Fraunhofer Institute for Laser Technology ILT in Aachen, Germany. The researcher and his team have now managed to erase the previous boundaries of laser welding.

“The industry now also makes infrared absorbers that are nearly transparent, but these are not only very expensive but also have a green, yellowish tint to them,” Olowinsky elaborates. “So our goal was to find a way to get the job done completely free of absorber materials.” To accomplish this, researchers studied the absorption spectra of a range of transparent polymers in search of wavelength ranges within which plastic absorbs laser radiation. Then the scientists tested and perfected the laser systems to match: systems that emit light of the right wavelengths. “Before, you didn’t have the right light source,” Olowinsky adds. “It was only during the past few years that laser sources have been developed that emit light in these wavelength ranges.” To deliver the light energy to the joining level – to the seam along the border between the two transparent plastics – the experts at ILT came up with special lens systems. These systems focus the beam so that the highest energy density occurs at the beam waist – where the beam diameter is the smallest – so that the highest temperature is delivered precisely to the joining level.

The researchers’ most promising results were achieved at a wavelength of around 1700 nanometers. “This is the peak welding-efficiency range,” Olowinsky summarizes. Nevertheless, the researchers are also continuing work on the EU Commission-sponsored “PolyBright” project (www.polybright.eu) in search of the combination of the right absorption bands with the matching light sources. “The result has to be the most cost-effective laser system possible that can execute high-precision welding tasks at the highest possible speed.”

Medical technology and bioanalytics in particular are among the main beneficiaries of the new welding process: The magic word is “lab on a chip.” This refers to automatic, miniature-sized laboratory analysis on the surface of a chip. Whether fluids, protein or DNA analyses – the spectrum of applications is a broad one.

(Photo: © Fraunhofer ILT)

Fraunhofer ILT


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Quantum mechanics, developed in the 1920s, has had an enormous impact in explaining how matter works. The elementary particles that make up different forms of matter — such as electrons, protons, neutrons and photons — are well understood within the model quantum physics provides. Even now, some 90 years later, new scientific principles in quantum physics are being described. The most recent gives the world a glimpse into the seemingly impossible.

Prof. Eran Rabani of Tel Aviv University's School of Chemistry and his colleagues at Columbia University have discovered a new quantum mechanical effect with glass-forming liquids. They've determined that it's possible to melt glass — not by heating it, but by cooling it to a temperature near Absolute Zero.

This new basic science research, to be published in Nature Physics, has limited practical application so far, says Prof. Rabani. But knowing why materials behave as they do paves the way for breakthroughs of the future. "The interesting story here," says Prof. Rabani, "is that by quantum effect, we can melt glass by cooling it. Normally, we melt glasses with heat."

Classical physics allowed researchers to be certain about the qualities of physical objects. But at the atomic/molecular level, as a result of the duality principle which describes small objects as waves, it's impossible to determine exact molecular position and speed at any given moment — a fact known as the "Heisenberg Principle." Based on this principle, Prof. Rabani and his colleagues were able to demonstrate their surprising natural phenomenon with glass.

Many different materials on earth, like the silica used in windows, can become a glass — at least in theory — if they are cooled fast enough. But the new research by Prof. Rabani and his colleagues demonstrates that under very special conditions, a few degrees above Absolute Zero (−459.67° Fahrenheit), a glass might melt.

It all has to do with how molecules in materials are ordered, Prof. Rabani explains. At some point in the cooling phase, a material can become glass and then liquid if the right conditions exist.

"We hope that future laboratory experiments will prove our predictions," he says, looking forward to this new basic science paving the way for continued research.

The research was inspired by Nobel Prize winner Philip W. Anderson, who wrote that the understanding of classical glasses was one of the biggest unsolved problems in condensed matter physics. After the challenge was presented, research teams around the world rose to it.

Until now, structural quantum glasses had never been explored — that is, what happens when you mix the unique properties in glass and add quantum effects. Prof. Rabani was challenged to ask: if we looked at the quantum level, would we still see the hallmarks of a classical glass?

What the researchers unearthed is a new and unique hallmark, showing that quantum glasses have a unique signature. Many materials he says can form a glass if they're cooled fast enough. Even though their theory is not practical for daily use: few individuals own freezers that dip down nearly 500 degrees below zero.

(Photo: TAU)

Tel Aviv University


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Rare fragments of Martian meteorites have been investigated at the University of Leicester revealing one of the ways water flowed near the surface of Mars.

Scientists at the University's renowned Space Research Centre, in the Department of Physics and Astronomy, examined five meteorite samples – including the very first nakhlite, found a century ago.

Nakhlites are a form of meteorite known to have originated on Mars. They are named after the village of El-Nakhla in Egypt where the first one was found in 1911.

Findings from the research have been published in Meteoritics and Planetary Science (Dec. 2010 issue, vol 45). The research was funded by the Science and Technology Facilities Council (STFC).

Hitesh Changela and Dr John Bridges used electron microscopes in the University's Advanced Microscopy Centre to study the structure and composition of five nakhlites, including the 1911 specimen, which is housed in the collections of the Natural History Museum, London. Minute wafers of rock, about 0.1 microns thick, were milled off the meteorites as part of the research.

By comparing the five meteorites, they showed the presence of veins created during an impact on Mars. They suggest that this impact was associated with a 1-10 km diameter crater. Buried ice melted during this impact depositing clay, serpentine, carbonate and a gel deposit in the veins.

This work closely ties in to recent geological discoveries of clay and carbonate on the surface of Mars made by NASA and ESA probes, and shows how some of it probably formed. Serpentine mineralisation is associated with the production of methane. It is the purpose of the 2016 Trace Gas Orbiter mission to search for and understand the origin of any methane in the Mars atmosphere as it can be a biomarker. This work shows one of the ways that methane was probably produced.

Dr Bridges, who is supervising Hitesh's PhD, said, "We are now starting to build a realistic model for how water deposited minerals formed on Mars, showing that impact heating was an important process. The constraints we are establishing about temperature, pH and duration of the hydrothermal action help us to better understand the evolution of the Mars surface. This directly ties in with the current activities of landing site selection for Mars rovers and Mars Sample Return. With models like this we will better understand the areas where we think that water was once present on Mars.

(Photo: University of Leicester)

University of Leicester




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