What’s more, car owners are predicted to cut back on driving in order to save money. Together, these changes in consumer behaviour could make an important dent in the US contribution to global warming, reducing annual carbon dioxide emissions by tens of millions of tonnes per year. The impact will be dramatic, says Chris Knittel, an economist at the University of California, Davis, who was involved in one of the studies.

The changes are being driven by record fuel prices in the US, where, at the end of April, the average price of gasoline stood at $3.65 per gallon, 20 percent more than in January and treble the price of a decade ago. Until recently, these increases did not seem to be having a consistent effect on the car market and fuel use. Though sales of SUVs in the US have been falling over the past few years, this decline has come on the back of years of rapid growth, and overall gasoline consumption has been increasing every year since 1991.

That could be about to change. Knittel and colleagues looked at data on 1.4 million car purchases over the past 10 years, comparing sales patterns with gas prices. They found that sales of the least fuel-efficient cars, such as SUVs and pick-up trucks, fell by 13 percent for every $1 per gallon increase in the price of gasoline. The biggest SUVs suffered the most, with sales dropping by over 25 percent for every dollar by which the gas price rose. And for every $1 hike in gas prices there was a corresponding 17 percent sales boost for the most efficient vehicles, such as compact cars and hybrids. Knittel estimates that over about a decade, such changes in buying habits could cut the amount of gasoline used by US drivers by around 7 percent for every $1 increase in its price.

Knittel’s findings, presented last month at the University of California Energy Institute in Berkeley, are in broad agreement with those of economist Kenneth Small of the University of California, Irvine. Small looked at data on US fuel consumption and prices over the past 40 years, and projected last year that the recent doubling in fuel prices would quickly lead to a 4 percent drop in the total mileage covered on the roads. In the longer term, as drivers continue to react to rising prices, he projects the size of the reduction will grow to around 20 percent (The Energy Journal, vol 28, p 25).

This would lead to a substantial reduction in carbon emissions. Small says that a $1 per gallon rise in gasoline prices, roughly that seen over the past two years, will result in motorists using 14 percent less fuel in the long term. That would avoid the release of some tens of millions of tonnes of CO2 per year, equivalent to roughly 2 percent of the country’s greenhouse-gas emissions for 2006. That is a hugely significant drop, close to the level of cuts that some nations are required to make under the Kyoto protocol.

Small’s prediction comes with major caveats, however. Gasoline prices are not expected to return to the lows of a decade ago, but could fall by 10 or 20 percent in coming years. And any US economic recovery will boost fuel consumption, partly through raising incomes, which would dilute the pressure on motorists to drive less. So while expensive fuel will rein in consumption, Small and other economists question whether this will be enough to cause an overall fall in emissions from cars.

It is also possible that politics will intervene before any of these effects has a chance to kick in. Presidential hopefuls John McCain and Hillary Clinton have reacted to consumer protests over soaring fuel prices by declaring that they would suspend federal gasoline taxes. “It’s a fantastically stupid idea,” says Roberton Williams, an economist at the University of Texas at Austin.

“But people don’t like high gas taxes, so it’s popular.”

[Claire Bowles @ New Scientist]

Among the most important and complex molecules in the human body, sugars control not just metabolism but also how cells communicate with one another. Graduating senior Jeffery Martin has put his basic knowledge of sugars to exceptional use by creating a lab-on-a-chip device that builds complex, highly specialized sugar molecules, mimicking one of the most important cellular structures in the human body — the Golgi Apparatus.

“Almost completely independently he has been able to come closer than researchers with decades more experience to creating an artificial Golgi,” said Robert Linhardt, the Ann and John H. Broadbent Jr. ‘59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer and Martin’s adviser. “He saw a problem in the drug discovery process and almost instantly devised a way to solve it.”

Cells build sugars in a cellular organelle known as the Golgi Apparatus. Under a microscope, the Golgi looks similar to a stack of pancakes. The strange-looking organelle finishes the process of protein synthesis by decorating the proteins with highly specialized arrangements of sugars. The final sugar-coated molecule is then sent out into the cell to aid in cell communication and to help determine the cell’s function in the body.

Martin’s artificial Golgi functions in a surprisingly similar way to the natural Golgi, but he gives the ancient organelle a very high-tech makeover. His chip looks similar to a miniature checker board where sugars, enzymes, and other basic cell materials are suspended in water and can be transported and mixed by applying electric currents to the destination squares on the checker board. Through this process sugars can be built in an automated fashion where they are exposed to a variety of enzymes found in the natural Golgi. The resulting sugars can then be tested on living cells either on the chip or in the lab to determine their effects. With the chip’s ability to process many combinations of sugars and enzymes, it could help researchers quickly uncover new sugar-based drugs, according to Martin.

Scientists have known for years that certain sugars can serve as extremely beneficial therapeutics for humans. One well-known example is heparin, which is among the most widely used drugs in the world. Heparin is formed naturally in the Golgi organelle in cells of the human body as well as in other animals like pigs. Heparin acts as an anticoagulant preventing blood clots, which makes it a good therapeutic for heart, stroke, and dialysis patients.

The main source of heparin is currently the intestines of foreign livestock and, as recent news reports highlight, the risk of contamination from such sources is high. So researchers are working around the clock to develop a safer, man-made alternative to the drug that will prevent outside contamination. A synthetic alternative would build the sugar from scratch, helping eliminate the possibility of contamination he explained.

“I am very grateful to have the privilege of working with Dr. Linhardt who has discovered the recipe to make fully synthetic heparin,” Martin said. “Because we know the recipe, I am going to use it as a model to test the device. If our artificial Golgi can build fully functional heparin, we can then use the artificial organelle to produce many different sugar variants by altering the combination of enzymes used to synthesize them. Another great thing about these devices is that they are of microscale size, so that if needed we could fill an entire room with them to increase throughput for drug discovery.”

There are millions of possible sugar combinations that can be formed and scientists currently only know the function of very few of them like heparin. “Since it is known that these types of sugars play a part in many important biological processes such as cell growth, cell differentiation, blood coagulation, and viral defense mechanisms, we feel that that this artificial Golgi will help our team to develop a next generation of sugar-based drugs, known as glycotheraputics,” Martin said. “We are going to start making new combinations and we simply don’t know what we are going to find. We could find a sugar whose signal blocks the spread of cancer cells or initiates the differentiation of stem cells. We just don’t know.”

Martin, a Barry M. Goldwater Scholar and native of the small town of Boylston, Mass., is graduating from Rensselaer on May 17, 2008 with a nearly perfect GPA. He plans to continue on at Rensselaer as a graduate student, working with Linhardt to test and further develop his artificial Golgi.

[Gabrielle DeMarco @ Rensselaer Polytechnic Institute]

By JOHN GEROME Sunday, May 11, 2008 Carrie Underwood is the newest member of the Grand Ole Opry. via WQXI-AM Atlanta

Though antiretroviral “cocktails” can target an active infection, they cannot get at the virus when it retreats inside the host’s T cells, where it may lie dormant for decades, waiting for an opportunity to burst forth in a fresh round of infection. What HIV hunters need is a good bird dog.

Now, Stanford chemist Paul Wender and his coworkers have found a way to synthesize better bird dogs, agents that can be tailored to flush HIV out into the open where the immune system and antiretroviral therapies can destroy it. Wender is senior author of a paper about the research in the May 2 issue of Science.

“We’re not sure how far this will go, but certainly, from a theoretical point of view, it has promise of taking therapy to the next level???that is, addressing issues related to eradication of the disease, of the virus, at least,” said Wender, the Francis W. Bergstrom Professor.

Wender and his co-workers Jung-Min Kee and Jeff Warrington have developed a way to synthesize prostratin and DPP, two compounds that occur naturally in plants, in the laboratory. Prostratin, found in the Mamala plant (Homalanthus nutans) that grows in the Samoan rainforest, has shown promise in previous studies as an activator of dormant HIV. DPP, a molecular relative of prostratin found in resin spurge (Euphorbia resinifera), which grows in arid regions, also has shown potential.

Research has been hampered, though, because the compounds are difficult to obtain, particularly in the quantities needed for practical lab work on their mode of action and therapeutic potential. The yield from both plants is low and highly variable; the availability of the plants is limited; and isolating the compound is difficult. Heavy harvesting of the wild plants, especially in Samoa, also could cause ecological damage.

But synthetic prostratin and DPP, which now can be readily made in the lab, changes that equation.

“We have now minimized, if not eliminated, the issue of availability of prostratin and DPP,” Wender said. “But equally, if not more importantly, we have opened access to other compounds that might be similar in structure but superior in function.”

Previous work done in mice by researchers at the University of California-Los Angeles indicates that prostratin, used in combination with interleukin-7, an immune system stimulator made in bone marrow, managed to flush out and eliminate approximately 80 percent of the dormant virus. But with HIV, 80-percent efficiency is not enough. Anything less than 100 percent means the virus is still lurking in the T-cells and will spring back to action as soon as an opportunity presents itself.

“Nature has produced these compounds for various reasons in the plants from which they’re derived, but certainly not to treat human maladies,” Wender said. “They’re not optimized for human therapy.”

But with synthetic prostratin and DPP available, researchers can take the basic compounds and tinker with the structure and related function. “We could find out how to improve them by reverse engineering: figuring out what is important and what isn’t important,” Wender said. “We could begin to design and synthesize molecules that would never be found in nature but might actually be therapeutically more beneficial than what has been found thus far.”

In the Science paper, Wender and his team detail how both compounds can be synthesized, but also show the initial phase of designing and making new derivative compounds.

Although prostratin has long been used by traditional Samoan healers without their patients experiencing acute side effects, it is possible that undesirable effects could show up in an immune-impaired patient taking prostratin or DPP. But Wender noted that engineering the compounds in a lab would permit scientists to circumvent these problems. “Usually these kinds of side effects are a result of a drug hitting multiple targets. So it hits one target, which is beneficial, but then it hits some other target, too,” he said. “But by modifying the structures, you could select for the beneficial activity over the non-beneficial activity.”

“It’s a little bit like draw poker,” Wender said. “The important point is that we’re not forced to use the hand we get. We’ll get a hand and we’ll return a few cards if we don’t like it, because we can keep on tuning this until we get it right, so that a royal flush, hopefully, can be realized.”

Wender’s team developed their method of synthesizing prostratin and DPP by using a renewable resource, croton oil, made from the seeds of a small tree (Croton tiglium) cultivated in Asia. They derived phorbol from the croton oil and then converted it into the structure of prostratin.

The conversion process required some engineering finesse; they had to overcome a hurdle when, by removing an oxygen atom, they triggered a series of anticipated but seemingly undesired changes.

“To the credit of my coworkers, Jung-Min Kee and Jeff Warrington, they employed a strategy that sometimes is missed,” Wender said. “Rather than fighting the flow, they went with it.” They found a way to redirect the chemical complications into a solution to the problem that proved even better than the route they had initially sought to follow.

“Eventually they produced a shorter, more economical way of connecting our starting material, phorbol, to our target, prostratin,” Wender said. The process Kee and Warrington came up with requires only five steps, which is of tremendous importance in making it economically feasible. As Wender pointed out, “steps cost money and human time.”

Wender emphasized that the work of his team is the most recent chapter in efforts of a truly global community, starting with the Samoan healers, who willingly shared their knowledge with Paul Cox, an ethnobotanist who saw them prescribing a tea made from Mamala bark for patients with hepatitis-like symptoms. Cox, in turn, sent samples to the National Institutes of Health, in hopes that the bark might have antiviral properties useful in fighting some cancers. Researchers at NIH then analyzed the bark and isolated prostratin.

Prostratin belongs to a class of compounds called tiglianes, many of which promote tumor growth, so it had no initially perceived use in fighting cancer. But NIH researchers found that prostratin was not a tumor promoter and checked to see if perhaps it could help combat HIV, which is when its remarkable ability to flush out the dormant virus was discovered. Significantly, prostratin has also been found to block uptake of the purged virus, offering yet another potentially therapeutic benefit.

“The whole effort is a testimonial to a global community working to deal with what I think is a global, and top priority, problem,” Wender said.

The research was funded by the National Institutes of Health. At the time of the study, Kee was a doctoral candidate in chemistry and Warrington was a postdoctoral scholar at Stanford. Kee is now a postdoctoral scholar at Rockefeller University, and Warrington is working in the biotech industry.

The Joint United Nations Programme on HIV/AIDS estimates that 33.2 million people were living with HIV and 2.1 million people lost their lives to AIDS in 2007. Current antiviral therapies require lifelong treatment, and patients must consistently take doses of medication on a precise schedule, which creates compliance challenges for many of them. The antiviral drugs often become ineffective as the virus develops resistance and are exceptionally costly, the last a major problem in less-developed regions of the globe.

[Louis Bergeron @ Stanford University]