High Cholesterol protects against Infections

A very good read..Many researchers have suggested that the blood lipids play a key role in the immune defence system. There is also a growing understanding that an inflammatory response of the arterial intima to injury is a crucial step in the genesis of atherosclerosis. and that infections may be one type of such injury.22 These two concepts are difficult to harmonize with the low-density-lipoprotein (LDL) receptor hypothesis, according to which high LDL cholesterol is the most important cause of atherosclerosis. However, the many observations that conflict with the LDL receptor hypothesis, may be explained by the idea that high serum cholesterol and/or high LDL is protective against infection and atherosclerosis.

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Old Genes Can Learn New Tricks, Horned Beetles Show

A popular view among evolutionary biologists that fundamental genes do not acquire new functions has been challenged by a new study in the Proceedings of the National Academy of Sciences.

Indiana University Bloomington biologist Armin Moczek and research associate Debra Rose report that two ancient genes were "co-opted" to help build a new trait in beetles -- the fancy antlers that give horned beetles their name. The genes, Distal-less and homothorax, touch most aspects of insect larval development, and have therefore been considered off-limits to the evolution of new traits. In the two horned beetle species Moczek and Rose studied, the genetic sequences of Distal-less and homothorax were hardly different, suggesting the two genes have retained their unique identities because of selective pressures not to change. What changed was not the genes themselves, but when and where they are turned on.

"Evolutionary biologists have a good idea of what it takes to change the shape of a wing, the length of a leg, or the anatomy of an eye," Moczek said. "What we have struggled with, though, is how these traits originate in the first place. How do you evolve that first wing, limb or photoreceptor from a flightless, limbless and blind ancestor?"

To investigate these questions, Moczek and Rose examined three development genes that are so old, all insects have them: Distal-less, homothorax and a third, dachshund. The genes were first characterized in fruit flies, and are categorized as "upstream" regulatory genes because they influence a wide variety of genetic processes in insect cells, such as the development of legs, antennae and wings. Moczek said that in horned beetles, each of the three genes is likely to have hundreds to thousands of downstream targets.

A tenuous consensus among evolutionary biologists was that such genes -- upon which so many different and important processes depend -- could not be easily modified, because any modification would affect countless aspects of the insect's development, any one of which could be bad for the individual insect, reducing its fitness relative to its peers.

Moczek and Rose's PNAS paper confirms one aspect of this idea. All three genes were sequenced and found to be highly conserved, or unchanged, not only among the individuals of each beetle species they examined, but also between the two species, Onthophagus taurus (Italy) and Onthophagus binodis (South Africa), whose lineages diverged about 24 million years ago. But that isn't the whole story.

To understand the effects of the three genes on horned beetle development, Moczek and Rose employed a new and promising technique, RNA interference, which disables the action of specific genes without compromising other genetic processes. Humans are only mimicking nature here; RNA interference is also a natural method of gene regulation in eukaryotes.

Moczek and Rose divided beetle larvae of both species into three treatment groups: no injection, buffer injection with nonsense RNA and buffer injection with RNA interference transcripts designed to disrupt one of three crucial developmental genes.

Moczek and Rose learned that two of the three genes, Distal-less and homothorax, are used by both O. taurus and O. binodis in the development of beetle horns. While Distal-less was found to affect both the development of thorax horns (which form just behind the head) and head horns, homothorax was only found to influence thorax horn development. The gene dachshund appears to have no effect whatsoever on horn development in either species.

"The evolution of novel features does not require the evolution of novel genes," Moczek said. "A lot of innovation can grow from within the organism's genetic toolbox."

More importantly, Moczek and Rose learned all developmental genes are candidates for such recruitment, not just the genes whose development functions are considered non-essential or limited in their effects.

Moczek also says the PNAS paper may compel evolutionary biologists to revisit pleiotropy, the foundational concept of one gene influencing many traits.

"It may be that our understanding of pleiotropy is too simplistic," Moczek said. "Now that we know fundamental development genes can acquire new and diverse functions with relative ease, pleiotropy may not be nearly as constraining as we have thought."

U.S. company finds "safer" way to make stem-like cells

U.S. researchers said on Thursday they had come up with the safest way yet to make stem-like cells using a patient's ordinary skin cells, this time by using pure human proteins. The team at Harvard University and Massachusetts-based Advanced Cell Technology Inc said their technique involves soaking cells in human proteins that turn back the clock biologically, making the cells behave like powerful embryonic stem cells.

Dr. Robert Lanza of Advanced Cell sees almost immediate commercial applications.

"After a few more flight tests -- in order to assure everything is working properly -- it should be ready for commercial use," Lanza said by e-mail.

He said the company would seek Food and Drug Administration permission to test the cells in people by next year -- a process unlikely to be quick, especially with a brand-new technology such as this one.

Stem cells are the body's master cells, giving rise to all the tissues, organs and blood. Embryonic stem cells are considered the most powerful kind, as each one is pluripotent, with the potential to morph into any type of tissue.

Doctors hope to someday use them to transform medicine, for instance, by regenerating the cells destroyed in type 1 diabetes or regrowing eye cells to reverse blindness.

But embryonic cells require the use of an embryo or cloning technology, and several countries, including the United States, limit funding for such experiments.

Several teams of scientists have homed in on four genes that can turn back the clock in ordinary cells, making them look and act like embryonic stem cells. These so-called induced pluripotent stem cells, or iPS cells, could in theory be made using a patient's own skin, allowing grow-your-own transplants with no risk of rejection.

DIFFICULT WORK

Getting these genes into the cells is not easy, however.

The first attempts used retroviruses, which integrate their own genetic material into the cells they infect. Others used loops of genetic material called plasmids or other genetically engineered molecules to reformat the cells.

And another team used the proteins made by the four genes and valproic acid to reprogram cells, but Lanza said these methods all have drawbacks.

His team, working with Kwang-Soo Kim of the Harvard Stem Cell Institute and a team at CHA Stem Cell Institute in South Korea used a peptide, a protein fragment, to drag the human proteins into the cells.

"These have been around for a long time," Lanza said. "The AIDS virus uses the peptide to get into the cells it infects," he said.

Using cells from the foreskins of newborn boys -- a common laboratory technique -- they showed they could transform the cells into iPS cells. They regrew them into a variety of mature new cell types, they reported in the journal Cell Stem Cell.

"This method eliminates the risks associated with genetic and chemical manipulation, and provides for the first time a potentially safe source of iPS cells for translation into the clinic," Lanza said.

"This is the ultimate stem cell solution -- you just add some proteins to a few skin cells and voila! Patient-specific stem cells!"

One question that is not clear is who owns the technology. Lanza said many groups have tried to patent the various steps in the process and it is not yet clear whose patents will prevail.