Wednesday, March 24, 2010

ASU SCIENTISTS NARROW DOWN ORIGINS OF MALARIA

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From King Tut to Alexander the Great to Mother Theresa, the mosquito-borne illness malaria has long been a menace to human civilization. Now, an international team of scientists, including Arizona State University School of Life Sciences professor Ananias Escalante, has attempted to better understand this scourge by tracing it back to its earliest origins.

In the largest study of its kind, Escalante, a researcher in the Biodesign Institute’s new Center for Evolutionary Medicine and Informatics, along with colleagues from 15 leading international institutions, looked at the origins of Plasmodium falciparum, the protozoa species that causes the majority of human malaria cases. The team examined the root cause of malaria amongst populations of chimpanzees, our closest primate relative, because infectious agents often become opportunistic, and over time, can leap from one species to another, with devastating consequences.

"This research is an example of our long-term goal: establishing bridges among the anthropological, epidemiological, ecological, and evolutionary biology perspectives to address the origin and dynamic of infectious diseases," said Escalante.

By comparing the genetic sequences of the malaria culprit that infected two closely related wild chimpanzee species and bonobos, the team hoped to uncover the genetic origins of malaria. They found high levels of infection in the wild chimps. Their data has also reshaped the current thinking on the animal origins of human malaria. Results suggest that P. falciparum did not originate from chimpanzees (Pan troglodytes), but rather evolved in bonobos (Pan paniscus), from which it jumped to humans. The malaria infections found in bonobos do not seem cause any harm or illness to the animals.

“This is a very important study, because species origins of human diseases are critical to deciphering factors, genetic and social, that make such transfers possible,” said Sudhir Kumar, director of the Center for Evolutionary Medicine and Informatics. Disease origins is a major research theme in this Biodesign center, and professor Escalante leads research and development efforts in this area.

"The finding of a number of “falciparum”-like species raises important and addressable questions about the mechanisms involved in the success of P. falciparum as a human parasite that may well be applicable to disease control," Escalante said.

Armed with new information, the team hopes to use this knowledge in the current battle to control malaria. With a detailed knowledge of the genetic underpinnings of this illness, that team may help to identify the genes responsible for eluding the human immune system or guide the development of new treatment strategies for this global threat to human health.

(Photo: ASU)

Arizona State University

ROVING SONIC HEDGEHOG GENE MAY CHANGE SCIENTISTS UNDERSTANDING OF LIMB GROWTH

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Sonic hedgehog, a gene that plays a crucial rule in the positioning and growth of limbs, fingers and toes, has been confirmed in an unexpected place in the embryos of developing mice — the layer of cells that creates the skin.

Named for a video game character, Sonic hedgehog describes both a gene and the protein it produces in the body. Its study is important to increase understanding of human birth defects.

It was thought to be exclusively present in the cell layer that builds bone and muscle, called the mesoderm. But University of Florida Genetics Institute researchers have discovered that Sonic hedgehog is also at work in mice limb buds in what is known as the ectoderm, the cell layer that gives rise to the skin in vertebrates.

Finding Sonic hedgehog in this layer of cells is loosely akin to discovering that yeast has crept from the batter to the frosting, where it has the surprising effect of limiting how much the cake will rise. More literally, instead of causing appendages to grow, Sonic hedgehog seems to act as a failsafe mechanism to keep additional digits from developing.

“Sonic hedgehog protein determines how your limbs form, and why your pinky is at the bottom of your hand and your thumb is at the top,” said Brian D. Harfe, an associate professor of molecular genetics and microbiology at the UF College of Medicine. “But what’s been previously published is only part of the picture. We determined that Sonic hedgehog signaling is required in the ectoderm to have normal digit formation. Get rid of it, and an extra digit forms.”

In this case, when scientists disrupted Sonic hedgehog signaling in a small region of the limb buds of embryonic mice, an additional digit began to arise in what would be the mouse paw.

The discovery, to appear online in Proceedings of the National Academy of Sciences, suggests that Sonic hedgehog’s role in the growth of appendages is far more complex than originally thought. Developmental biologists may have to rethink established theories about how limbs are patterned in vertebrates — an effort that could provide insight into human birth defects.

“We used technology where a viral protein seeks out specific sequences of DNA,” said Cortney M. Bouldin, a graduate student in the Interdisciplinary Program in Biomedical Sciences in the department of molecular genetics and microbiology. “We concentrated on disabling a protein essential for Sonic hedgehog signaling. Although it has been removed from the limb before, we wanted to specifically remove it from the ectoderm. When we did that, in the latter stages of development, we saw extra cartilage and the early beginnings of another digit.”

Sonic hedgehog signaling in the ectoderm of limb buds may act as a buffering system that prevents unneeded growth, Bouldin said.

The UF research was sparked by studies of gene activity in the limb buds of mice by William J. Scott, a professor of pediatrics at the University of Cincinnati. Scott used a microarray experiment to examine gene expression levels in the ectoderm of mice limb buds, finding activity that could not be possible without the presence of Sonic hedgehog.

UF researchers were able to advance this investigation from cell studies to developing mice embryos by knocking out gene expression in a small region of the ectodermal layer. It allowed them to observe early limb development in the absence of Sonic hedgehog signaling.

“The view had been if you reduce signaling, if anything you would get fewer fingers,” said Scott, who did not participate in the UF research. “We now know we can’t disregard Sonic hedgehog signaling in the ectoderm. It still has its predominant effect in the tissue where it is made, but it does something more than we thought it did previously. When we try to understand problems that arise with limb growth in humans, we will be able to examine those possibilities.”

Harfe said the next phase of the work will be to observe what happens when Sonic hedgehog signaling is disrupted through larger segments of the ectodermal layer. Ultimately, researchers hope the work will lead to quality of life improvements for people.

“We would like to repair limb defects in humans and enhance regeneration of limbs, helping people who might cut off fingers in an accident, for example,” Harfe said.

(Photo: Anney Doucette)

University of Florida

STRENGTH IS SHORE THING FOR SEA SHELL SCIENTISTS

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A team of materials scientists and chemists have taken inspiration from sea shells found on the beach to create a composite material from dissimilar ‘ingredients’.

Their technique could be used to make ceramics with high resistance to cracking – which could in turn be used in crack-resistant building materials and bone replacements.

Writing in the journal Advanced Materials, scientists from The University of Manchester and The University of Leeds report that they have successfully reinforced calcium carbonate, or chalk, with polystyrene particles that are used to make drinks cups.

They have developed an effective method of combining calcite crystals with polystyrene particles – and have found this makes the material more ductile compared to its original brittle form.

They report that the polystyrene also acts as a toughening agent, assisting the prevention of the growth of cracks.

Scientists also observed that when the reinforced material cracked, the polymer lengthened within the cracks – a well-known mechanism for absorbing energy and enhancing toughness.

Researchers say their method allows the properties of the new material to be tweaked by selecting particles of different shapes, sizes and composition.

Dr Stephen Eichhorn from The School of Materials at The University of Manchester, said: “The mechanical properties of shells can rival those of man-made ceramics, which are engineered at high temperatures and pressures. Their construction helps to distribute stress over the structure and control the spread of cracks.

“Calcium carbonate is the main ingredient of chalk, which is very brittle and breaks easily when force is applied. But shells are strong and resistant to fracturing, and this is because the calcium carbonate is combined with proteins which bind the crystals together, like bricks in a wall, to make the material stronger and sometimes tougher.

“We have replicated nature’s addition of proteins using polystyrene, to create a strong shell-like structure with similar properties to those seen in nature.

“Further research and testing is still needed but our research potentially offers a straightforward method of engineering new and tough chalk-based composite materials with a wide range of useful applications.”

The research was funded by grants from the Engineering and Physical Sciences Research Council (EPSRC) and was conducted in collaboration with Professor Fiona Meldrum in the School of Chemistry at the University of Leeds.

The University of Manchester

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