The platypus, classified as a mammal because it produces milk and is covered in a coat of fur, also possesses features of reptiles, birds and their common ancestors, along with some curious attributes of its own. One of only two mammals that lays eggs, the platypus also sports a duck-like bill that holds a sophisticated electrosensory system used to forage for food underwater. Males possess hind leg spurs that can deliver pain-inducing venom to its foes competing for a mate or territory during the breeding season.

“The fascinating mix of features in the platypus genome provides many clues to the function and evolution of all mammalian genomes,” says Richard K. Wilson, Ph.D., director of the The Genome Center at Washington University and the paper’s senior author. “By comparing the platypus genome to other mammalian genomes, we’ll be able to study genes that have been conserved throughout evolution.”

The platypus represents the earliest offshoot of the mammalian lineage some 166 million years ago from primitive ancestors that had features of both mammals and reptiles. “What is unique about the platypus is that it has retained a large overlap between two very different classifications, while later mammals lost the features of reptiles,” says Wes Warren, Ph.D., an assistant professor of genetics, who led the project.

Comparison of the platypus genome with the DNA of humans and other mammals, which diverged later, and the genomes of birds, whose ancestors branched off an estimated 315 million years ago, can help scientists fill gaps in their understanding of mammalian evolution. The comparison also will allow scientists to date the emergence of genes and traits specific to mammals.

The Nature paper analyzes the genome sequence of a female platypus named Glennie from New South Wales, Australia. The project was largely funded by the National Human Genome Research Institute, part of the National Institutes of Health, and includes scientists from the United States, Australia, England, Germany, Israel, Japan, New Zealand and Spain.

“At first glance, the platypus appears as if it was the result of an evolutionary accident,” says Francis S. Collins, M.D., Ph.D., director of NHGRI. “But as weird as this animal looks, its genome sequence is priceless for understanding how mammalian biological processes evolved.”

“While we’ve always been able to compare and consider all of these creatures on the basis of their physical characteristics, internal anatomy and behavior, it’s truly amazing to be able to compare their genetic blueprints and begin to get a close-up look at how evolution brings about change,” Wilson says.

As part of their analysis, the researchers compared the platypus genome with genomes of the human, mouse, dog, opossum and chicken. They found that the platypus shares 82 percent of its genes with these animals. The chicken genome was chosen because it represents a group of egg-laying animals, including extinct reptiles, which passed on much of their DNA to the platypus and other mammals over the course of evolution.

The researchers also found genes that support egg laying - a feature of reptiles - as well as lactation - a characteristic of all mammals. Interestingly, the platypus lack nipples, so its young nurse through the abdominal skin.

The researchers also attempted to determine which characteristics of the platypus were linked to reptiles at the DNA level. When they analyzed the genetic sequences responsible for venom production in the male platypus, they found it arose from duplications in a group of genes that evolved from ancestral reptile genomes. Amazingly, duplications in the same genes appear to have evolved independently in venomous reptiles.

The platypus swims with its eyes, ears and nostrils closed, relying on electrosensory receptors in its bill to detect faint electric fields emitted by underwater prey. Surprisingly, the researchers found the genome contains an expansion of genes that code for a particular type of odor receptor. “We were expecting very few of these odor receptor genes because the animals spend the majority of their life in the water,” Warren says.

Similar genes are found in animals that rely on a sense of smell, such as rodents and dogs, and the scientists suspect that their addition in the platypus allows the animals to detect odors while foraging underwater.

At roughly 2.2 billion base pairs, the platypus genome is about two-thirds the size of the human genome and contains about 18,500 genes, similar to other vertebrates. The animal has 52 chromosomes, including an unusual number of sex chromosomes: 10. The platypus X chromosome bears resemblance to the sex chromosome of a bird, known as Z.

Sequencing and assembling the platypus genome proved far more daunting than sequencing any other mammalian genome to date. About 50 percent of the genome is composed of repetitive elements of DNA, which makes it a challenge to assemble properly.

The platypus genome sequence, along with those for other organisms, such as the mouse, dog, cow, and many other animals can be accessed at GenBank (www.ncbi.nih.gov/Genbank) at NIH’s National Center for Biotechnology Information.

[Caroline Arbanas @ Washington University School of Medicine]

But it’s not just weight gain that poses a risk. People who are underweight also have an elevated risk of dementia, unlike people who are normal weight or overweight.

US researchers carried out a detailed review of 10 international studies published since 1995, covering just over 37,000 people, including 2,534 with various forms of dementia. Subjects were aged between 40 and 80 years when the studies started, with follow-up periods ranging from three to 36 years.

The review, which included studies from the USA, France, Finland, Sweden and Japan, also included a sophisticated meta-analysis of seven of the studies, published between 2003 and 2007 with a follow-up period of at least five years.

All kinds of dementia were included, with specific reference to Alzheimer’s Disease and to vascular dementia — where areas of the brain stop functioning because the blood vessels that supply them are damaged by conditions such as high blood pressure or heart disease.

“Our meta-analysis showed that obesity increased the relative risk of dementia, for both sexes, by an average of 42 percent when compared with normal weight” says Dr Youfa Wang, Associate Professor of International Health and Epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore.

“And being underweight increased the risk by 36 percent.

“But when we looked specifically at Alzheimer’s Disease, the increased risk posed by obesity was 80 percent. The increased risk for people with vascular dementia was 73 percent.

“The risks were greater in studies where sufferers developed Alzheimer’s Disease or vascular dementia before the age of 60 or in studies with follow-up periods of more than 10 years.

“We also found that obesity was more likely to be a risk factor for women when it came to developing Alzheimer’s Disease and for men when it came to vascular dementia.”

The authors estimate that 12 percent of the dementia risk in the study population could be attributed to obesity, with this rising to just over 21 percent in patients with Alzheimer’s Disease.

It’s estimated that up to 10 percent of people aged 65 or more suffer from some form of dementia and two-thirds of those have Alzheimer’s Disease.

“There has been controversy about the links between obesity and dementia for a number of years, but previous findings have been mixed and inconclusive” says Dr Wang.

“The advantage of carrying out a meta-analysis is that it provides researchers with access to a large number of study subjects and it is possible to iron out the inconsistencies and come to overarching conclusions.

“Our detailed analysis clearly shows a U-shaped relationship between weight and dementia, with people who are obese or underweight facing a greater risk.

“We believe that our results show that reducing the prevalence of obesity is a promising strategy for preventing the progression of normal ageing into Alzheimer’s Disease.”

[Annette Whibley @ Wiley-Blackwell]

The method, published in the May 4 issue of Nature Nanotechnology, enables more precise shaping of microchip components than what is possible with current technology. More precise component shapes could help manufacturers build smaller and better microchips, the key to more powerful computers and other devices.

“We are able to achieve a precision and improvement far beyond what was previously thought achievable,” said electrical engineer Stephen Chou, the Joseph C. Elgin Professor of Engineering, who developed the method along with graduate student Qiangfei Xia. Chou’s lab has previously pioneered a number of innovative chip making techniques, including a revolutionary method for making nanometer-scale patterns using imprinting.

Microchips work best when the structures fabricated on them are straight, thin and tall. Rough edges and other defects can degrade or even ruin chip performance in most applications. In integrated circuits, for instance, such flaws could cause current to leak and voltage to fluctuate. In optic devices, they could interfere with the transmission of light. In biological devices, they could impede the flow of DNA and other biomaterials.

“These chip defects pose serious roadblocks to future advances in many industries,” Chou said.

To deal with this problem, researchers try to improve the process used to make the microchips. However, Chou said such an approach works only to a point; eventually chip makers will run up against fundamental physical limits of current manufacturing techniques. In particular, the electrons and photons that are used like chisels to carve out the microscopic features on a chip always have some random behavior. This effect becomes pronounced at very small scales and limits the accuracy of component shapes.

“What we propose instead is a paradigm shift: Rather than struggle to improve fabrication methods, we could simply fix the defects after fabrication,” said Chou. ???And fixing the defects could be automatic — a process of self-perfection.???

Chou’s method, termed Self-Perfection by Liquefaction (SPEL), achieves this by melting the structures on a chip momentarily, and guiding the resulting flow of liquid so that it re-solidifies into the desired shapes. This is possible because natural forces acting on the molten structures, such as surface tension — the force that allows some insects to walk on water — smooth the structures into geometrically more accurate shapes. Lines, for instance, become straighter, and dots become rounder.

Simple melting by direct heating has previously been shown to smooth out the defects in plastic structures. This process can’t be applied to a microchip, for two reasons. First, the key structures on a chip are not made of plastic, which melts at temperatures close to the boiling point of water, but from semiconductors and metals, which have much higher melting points. Heating the chip to such temperatures would melt not just the structures, but nearly everything else on the chip. Secondly, the melting process would widen the structures and round off their top and side surfaces, all of which would be detrimental to the chip.

Chou’s team overcame the first obstacle by using a light pulse from so-called excimer laser, similar to those used in laser eye surgery, because it heats only a very thin surface layer of a material and causes no damage to the structures underneath. The researchers carefully designed the pulse so that it would melt only semiconductor and metal structures, and not damage other parts of the chip. The structures need to be melted for only a fraction of a millionth of a second, because molten metal and semiconductors can flow as easily as water and have high surface tension, which allows them to change shapes very quickly.

To overcome the second obstacle, Chou’s team placed a plate on top of the melting structures to guide the flow of liquid. The plate prevents a molten structure from widening, and keeps its top flat and sides vertical, Chou said. In one experiment, it made the edges of 70 nanometer-wide chromium lines more than five times smoother. The resulting line smoothness was far more precise than what semiconductor researchers believe to be attainable with existing technology.

The conventional approach to fixing chip defects is to measure the exact shape of each defect, and provide a correction precisely tailored to it — a slow and expensive process, Chou said. In contrast, Chou’s guided melting process fixes all defects on a chip in a single quick and inexpensive step. “Regardless of the shape of each defect, it always gets fixed precisely and with no need for individual shape measurement or tailored correction,” Chou said.

One of the big surprises from this work is observed when the guiding plate is placed not in direct contact with the molten structures, but at a distance above it. In this situation, the liquid material from the structures rises up and reaches the plate by itself, causing line structures to become taller and narrower — both highly desirable outcomes from a chip design perspective.

“The authors demonstrate improved edge roughness and dramatically altered aspect ratios in nanoscale features,” said Donald Tennant, director of operations at the NanoScale Science and Technology Facility at Cornell University. The techniques “may be a way forward when nanofabricators bump up against the limits of lithography and pattern transfer,” he said.

Next, Chou’s group plans to demonstrate this technique on large (8-inch) wafers. Several leading semiconductor manufacturers have expressed keen interest in the technique, Chou said.

[Steven Schultz @ Princeton University Engineering School]

Engineers at Duke University believe that the results of feasibility studies conducted in their laboratory represent the first concrete steps toward achieving this space age vision of the future. Also, on a more immediate level, the technology developed by the engineers could make certain contemporary medical procedures safer for patients, they said.

For their experiments, the engineers started with a rudimentary tabletop robot whose “eyes” used a novel 3-D ultrasound technology developed in the Duke laboratories. An artificial intelligence program served as the robot’s “brain” by taking real-time 3-D information, processing it, and giving the robot specific commands to perform.

“In a number of tasks, the computer was able to direct the robot’s actions,” said Stephen Smith, director of the Duke University Ultrasound Transducer Group and senior member of the research team. “We believe that this is the first proof-of-concept for this approach. Given that we achieved these early results with a rudimentary robot and a basic artificial intelligence program, the technology will advance to the point where robots — without the guidance of the doctor — can someday operate on people.”

The results of a series of experiments on the robot system directing catheters inside synthetic blood vessels was published online in the journal IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. A second study, published in April in the journal Ultrasonic Imaging, demonstrated that the autonomous robot system could successfully perform a simulated needle biopsy.

Advances in ultrasound technology have made these latest experiments possible, the researchers said, by generating detailed, 3-D moving images in real-time.

The Duke laboratory has a long track record of modifying traditional 2-D ultrasound — like that used to image babies in utero — into the more advanced 3-D scans. After inventing the technique in 1991, the team also has shown its utility in developing specialized catheters and endoscopes for real-time imaging of blood vessels in the heart and brain.

In the latest experiment, the robot successfully performed its main task: directing a needle on the end of the robotic arm to touch the tip of another needle within a blood vessel graft. The robot’s needle was guided by a tiny 3-D ultrasound transducer, the “wand” that collects the 3-D images, attached to a catheter commonly used in angioplasty procedures.

“The robot was able to accurately direct needle probes to target needles based on the information sent by the catheter transducer,” said John Whitman, a senior engineering student in Smith’s laboratory and first author on both papers. “The ability of the robot to guide a probe within a vascular graft is a first step toward further testing the system in animal models.”

While the research will continue to refine the ability of robots to perform independent procedures, the new technology could also have more direct and immediate applications.

“Currently, cardiologists doing catheter-based procedures use fluoroscopy, which employs radiation, to guide their actions,” Smith said. “Putting a 3-D ultrasound transducer on the end of the catheter could provide clearer images to the physician and greatly reduce the need for patients to be exposed to radiation.”

In the earlier experiments, the tabletop robot arm successfully touched a needle on the arm to another needle in a water bath. Then it performed a simulated biopsy of a cyst, fashioned out of a liquid-filled balloon in a medium designed to simulate tissue.

“These experiments demonstrated the feasibility of autonomous robots accomplishing simulated tasks under the guidance of 3-D ultrasound, and we believe that it warrants additional study,” Whitman said.

The researchers said that adding this 3-D capability to more powerful and sophisticated surgical robots already in use at many hospitals could hasten the development of autonomous robots that could perform complex procedures on humans.

[Richard Merritt @ Duke University]