DNA robots get sophisticated by Jef Akst

Scientists are one step closer to creating molecular robots that may eventually perform complex tasks, such as building nanomolecules or delivering drugs to target tissues.

They have constructed DNA-based robots that can walk along a specific path unaided or collect various nanoparticles along an assembly line, according to two studies published this week in Nature.

“This has the feel to me of the beginning of a technology revolution,” said Andrew Ellington, an evolutionary engineer at the University of Texas at Austin and the vice president of the International Society for Nanoscale Science, Computation and Engineering, who was not involved in the research. “This work will absolutely pave the way for how you build molecular robots.”

The robots built in one study are a type of DNA walker, called a molecular “spider.” They are minute, mobile molecules that move along a flat surface made out of folded DNA, known as DNA origami, binding to and unbinding from the surface as they go.

The movement of these spiders is largely random, however, said biochemist and study co-author Milan Stojanovic of Columbia University. But together with several other big players in the nanotechnology and DNA computing fields, including Nils Walter of the University of Michigan, Erik Winfree of the California Institute of Technology, and Hao Yan of Arizona State University, Stojanovic designed a DNA origami surface that directed the DNA spider down a specified path (see video).

“You just have to start it, and it walks the path,” said chemist Kurt Gothelf, director of Centre for DNA Nanotechnology at Aarhus University in Denmark, who was not involved in the research.

The spider is fueled by the chemical interactions its single-stranded DNA “legs” have with the origami surface. In order to take a “step,” the legs first cleave a DNA strand on the surface, weakening its interaction with that part of the origami surface. This encourages the spider to move forward, pulled towards the intact surface, where its interactions are stronger. When the spider binds to a part of the surface that it is unable to cleave, it stops.

In essence, the researchers created a DNA spider that can “sense the environment,” Stojanovic said — “molecules that respond [to environmental] cues and behave [in] certain programmable ways on their own.” The next step, he added, is to increase the complexity of movements performed by such autonomous robots by compiling “a collection of rules [of] interactions between molecules and between molecules and environment.”

A fluorescence video microscopy-generated animation of a DNA spider moving along the designated path from the green-labeled start site towards the red-labeled goal. Each colored dot represents its position at a given time over the 40-minute observation period (see legend).

Credit: Nils Walter, Anthony Manzo, Nicole Michelotti and Alexander Johnson-Buck, University of Michigan

Meanwhile, Nadrian Seeman of New York University and his colleagues have designed another type of DNA walker that can collect nano-sized “cargo” as it moves. Unlike the autonomous spider, the cargo-collecting walker is controlled by single strands of DNA added by the researchers to direct the robot. These strands instruct the robot to move past an “assembly line” of three small loading devices, also made out of DNA, each containing a gold nanoparticle. Each loading device can be programmed to either donate its cargo to the passing walker, or keep it, such that the walker can receive anywhere from zero to three particles along its short (less than 200 nanometers) journey.

It’s “like an automobile assembly line,” Seeman said. “We have the option to either add or not add various components to [the walker] depending on how the devices are programmed.”

One possibility for future experiments will be to combine the advances of each of the two papers into one complex, autonomous DNA robot, said Lloyd Smith of the University of Wisconsin, who wrote an accompanying review in Nature. “It’s going to take more work to take it to that next level, [but] bringing those two things together is going to be the next step towards” a fully autonomous, functional nano-sized robot.

Another future direction, the researchers agree, would be to scale up the length of the pathways and the complexity of the behaviors. But even once greater levels of complexity are achieved, what can actually be done with the little robots is still up for debate. “This whole field,” which is still in its early stages, Smith said, “hasn’t really found the application yet.” DNA robots have thus far proven to be capable of fairly sophisticated manipulation at the nanoscale, but the practical uses of this novel technology are still a little unclear.

One popular idea is to use cargo-collecting robots to construct nanomolecules that would be difficult to make using traditional methods, because of the control they offer researchers at such a tiny scale. “The ability to hold a molecule in a particular position and hold another molecule in a defined position could open up possibilities in organic synthesis,” said Smith. Another possibility is their use in drug delivery, said biochemist William Shih of Harvard University, who did not participate in the studies. “Having a very smart robotic delivery system could do a lot better job of killing the disease tissue and do far less damage to our otherwise healthy tissue,” he explained.

But most agree that these potential applications are yet to be realized; the current work merely shows “proof of principle” that such complex behavior might one day be achieved using this technology, Seeman said.

“I think these are both really, really significant papers, not because of what we can do with [these robots] now, but because of what we can do with them in the future,” said Ellington. They are “paving the way to a future where we can do practical DNA technology.”

H. Gu, et al., “A proximity-based programmable DNA nanoscale assembly line,” Nature, 465:202-5, 2010.

K. Lund, et al., “Molecular robots guided by prescriptive landscapes,” Nature, 465:206-10, 2010

Read more: DNA robots get sophisticated – The Scientist – Magazine of the Life Sciences http://www.the-scientist.com/blog/display/57400/#ixzz0oz3tm7it

Turmeric Extract Relieves Pain of Knee Osteoarthritis and Improves Function Comparably to Ibuprofen

February 16, 2010 by  
Filed under Arthritis, Blog

Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, Wattanamongkonsil L, Thamlikitkul V. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med. 2009;15(8): 891-897.

Osteoarthritis (OA), a degenerative joint disorder, is a common cause of disability for both men and women. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common treatment for pain relief associated with OA, they can cause serious adverse side effects that impact gastrointestinal, renal, and cardiac health. Curcumin present in turmeric (Curcuma longa syn. C. domestica) extracts has been reported to have anti-inflammatory and antioxidant properties. These authors, from Mahidol University in Bangkok, Thailand, conducted a study to determine the efficacy and safety of a turmeric extract in reducing pain and improving function in patients with knee OA.

Conducted at Siriraj Hospital in Bangkok from April 2005 to May 2006, the study included adult subjects with primary knee OA according to the American Rheumatism Association criteria. To be included in the study, patients had to have knee pain and radiographic osteophytes and at least 1 of the following characteristics: older than 50 years, suffering from morning stiffness lasting less than 30 minutes, and experiencing crepitus (crackling in joints) on motion. Patients reporting a pain score of ≥ 5 of 10 in a numerical rating scale were recruited.

The patients were asked to discontinue their medications for knee OA 1 week before randomization. All patients were randomly allocated to receive either ibuprofen (400 mg twice daily) or turmeric extract (500 mg curcuminoids 4 times daily) for 6 weeks.

According to the authors, the turmeric extracts were produced by the Thai Government Pharmaceutical Organization under the Good Manufacturing Practices standard. Dried rhizomes of C. longa were ground into powder. The turmeric powder was extracted with ethanol and then evaporated at low pressure to obtain ethanolic extracts containing oil and curcuminoids. The oil was then removed. Each capsule of extract contained 250 mg curcuminoids.

The patients were assessed every 2 weeks. The main outcomes were pain on level walking and pain on stair climbing, measured by a numerical rating scale, and knee functions assessed by the time spent on a 100-m walk and going up and down 10 steps.

All patients had blood tests including complete blood count, liver function, and renal function at week 0 and week 6. At week 6, the patients’ satisfaction with treatment was evaluated by a 5-category scale (high, moderate, little, same, or dissatisfaction).

Of 190 patients screened, 107 were selected for the study; 52 were randomly assigned to the curcuminoid group and 55 to the ibuprofen group. Of those, 45 patients in the curcuminoid group and 46 patients in the ibuprofen group completed the study. Most of the patients were overweight elderly women. The duration of symptoms before entering the trial was approximately 20 months. Half of the patients had bilateral knee OA. At baseline, the mean pain scores on level walking and on the stairs, as well as the time spent on the 100-m walk and on the flight of stairs, were similar between the 2 groups.

The authors report that in both groups, the mean scores of all outcomes at week 6 were significantly improved when compared with the baseline values. For example, from week 0 to week 6, the scores for pain on level walking dropped from 5.3 ± 2.3 to 2.7 ± 2.5 for the curcumin group and from 5.0 ± 1.9 to 3.1 ± 2.3 in the ibuprofen group. There was no significant difference in those parameters between the 2 groups, except that pain on stair climbing was less for those taking curcuminoids (P = 0.016). Also, the curcuminoid group seemed to spend less time on the 100-m walk and going up and down a flight of stairs. No significant differences were found for adverse events between the 2 groups, with dyspepsia (curcuminoids 20.8% and ibuprofen 26.9%) most common. Interestingly, many patients in the curcuminoid extract group who experienced bloating symptoms and passing gas described these symptoms as beneficial gastrointestinal effects, whereas those in the ibuprofen group reported gastrointestinal irritation symptoms.

Regarding satisfaction, most patients rated themselves as having moderate to high satisfaction (91.1% in the curcuminoid group and 80.4% in the ibuprofen group). The patients’ satisfaction with treatment was not statistically significantly different (P = 0.15) between the groups. The patients in the ibuprofen group had better compliance to the treatment regimen than those in the curcuminoid extract group (90.1% versus 82.8%, P = 0.001). This finding was attributed by the researchers to the fact that ibuprofen was given twice a day, whereas curcuminoid extract had to be taken 4 times a day.

These results suggest that curcuminoid extracts of turmeric might be as effective as ibuprofen in alleviating knee pain and improving knee functions, with a trend toward a greater effect in patients receiving curcumin extracts. However, the wide range of 95% confidence interval (CI) indicated that the study had an inadequate sample size. Based on the standard deviation (SD) of 2.36, the proper sample size should be 70 patients per group. The authors recommend more studies with an adequate sample, a higher dose of ibuprofen in the comparison group, and double-blind technique to demonstrate the efficacy of turmeric extracts in alleviating knee pain and improving knee function.

―Shari Henson

Source: American Botanical Council, 6200 Manor Rd, Austin, TX 78723
Phone: 512-926-4900 | Fax: 512-926-2345 | Email: abc@herbalgram.org

Nightshade Vegetables and Arthritis

June 10, 2009 by  
Filed under Arthritis, Blog

Did you know… that nightshade vegetables can exacerbate arthrititis and in some cases are the reason for arthritic type sign/symptoms. In many cases eliminating nightshade vegetables from the diet will alieviate signs and symptoms of arthritis within three weeks.

What are Nightshade Vegetables:

Tomatoes, peppers, eggplant, potatoes, garden huckleberry, ground cherries, and tobacco.

Nightshade vegetables contain solanine which is a glycoalkaloid.

Solanine is toxic if consumed in high doses which can result in the weakening of the bones and joints. It acts as an irritant which leads to inflammation at the nerve endings and joints.

Solanine is present in the green parts of the vegetable. For this reason, you may want to ensure that the green part is removed before consumption and select only ripe vegetables.  Stalk, stem and leaves should not be consumed. Cooking does not destroy solanine so you will need to be careful while consuming nightshade vegetables.

Nightshades and Arthritis:

Generally the body can mange the toxin levels present in fully ripened vegetables. However, arthritis causes stress on the body which can cause toxin levels to rise.  When nightshade vegetables are consumed, the solanine content exacerbates the toxicity which increases inflammation and ultimately pain in the joints. Therefore many arthritic patients complain about pain in their joints after consuming nightshade vegetables. Interestingly, the number of  diagnosed arthritis is higher in areas where nightshade vegetable consumption is more common.

Testing for Sensitivity to Nightshade Vegetables:

The best way to test is to first avoid all nightshades for at least one month.  If relief of joint pain is experienced, then sensitivity is likely.  Introducing one nightshade vegetable per day back into the diet is the best. Continuing elimination of nightshades that cause pain is necessary.

Living with Nightshade Sensitivities:

Complete elimination of nightshade vegetables is the easiest way to control your symptoms.  Make sure to check all labels for nightshade ingredients before consumption.

Check out www.noarthritis.com for more specific information.

Have arthritis? Need more specific information relating to your own situation?

Naturally Nutrition, Inc.

Specializing in Holistic Nutrition, Food Sensitivities and Celiac Disease

Orlando, Florida 32837

407 835-3353