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Science Feature Articles</p>

Lead Artifacts Disclose Their Age

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While reading about an ancient Roman technique for maneuvering heavy stones using lead lumps, Prof. Shimon Reich of the Weizmann Institute's Materials and Interfaces Department came up with an idea: The age of ancient lead could be determined with the help of superconducting properties.

 

To put his idea to work, he enlisted the help of a metallurgist -  Dr. Grigorii Leitus of the Weizmann Institute -  and an archaeologist, Dr. Sariel Shalev of Haifa University and the Weizmann Institute's Helen and Martin Kimmel Center for Archaeological Science.

 

The widespread dating method currently used in archaeology -  called radiocarbon dating -  works only for objects containing carbon, such as bone and wood. Until now, no archaeological method existed to directly date the lead (or other metal) artifacts, often found in archaeological excavations.

Prof. Shimon Reich. A matter of time

 

Reich's method makes use of the fact that lead corrodes very slowly and that the products of corrosion accumulate on its surface (since they don't easily dissolve in water). Finding out how much corrosion has developed will give a good indication of how old the lead is. Yet how can one determine the amount of corrosion products in a lead object without affecting the object?

 

This is where superconductivity comes in. When frozen to a temperature below -266 degrees Celsius (around -447 degrees Fahrenheit), lead, in contrast to its corrosion products, becomes a superconductor (meaning an ideal conductor of electricity). Lead superconductors repel magnetic fields about 100,000 times more strongly than their corrosion products. By measuring the magnetic properties of the frozen lead artifact, one can accurately deduce the amount of uncorroded lead in the artifact. Then, weighing the object, one measures the mass of the lead metal along with its corrosion products. The difference between the two values yields the amount of corrosion.

 

Testing lead artifacts whose age was already known (via the context in which they were found), the scientists constructed a graph that correlates archaeological age and amount of corrosion (per unit area). This graph will be used in the future to date archaeological lead artifacts of unknown age. The technique is useful for artifacts found in ground that is not very acidic.

 

The lead artifacts examined were taken from excavation sites in Caesaria and Tel Dor, and derive from three different periods. The oldest was from the Persian period, around 2,500 years ago.

 

The next artifacts to be tested by this method will be taken from sunken ships. In antiquity, lead was used extensively to prevent barnacles from attaching themselves on the hulls of ships. The method could thus prove useful in fixing the age of marine ruins that are otherwise hard to date.

 

Prof. Reich is the incumbent of the Robert W. Reneker Chair of Industrial Chemistry.

 
Prof. Shimon Reich. Superconductors as age detectors
Scientific Archaeology
English
Yes

Archaeological Riddles

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When a stone tablet containing a 15-line inscription apparently written by a Biblical king of Israel in the 9th century B.C.E turned up in the hands of an Israeli collector, it seemed a priceless treasure. An initial team of experts studying the "Jehoash tablet" declared it to be authentic. They based their conclusions on, among other things, radiocarbon dating conducted in a laboratory in Florida.

 
Radiocarbon dating measures the concentration of carbon, which can be found in two forms (i.e., isotopes): a common, stable form called C12 and a less common form called C14. The latter is radioactive and decays over time. Because the initial ratio of C14 to C12 is a given, and the radioactive C14 atom decays at a known rate, the age of an object can be deduced from comparing the ratio of C14 to C12.

Dr. Elisabetta Boaretto. Radiocarbon dating

Dr. Elisabetta Boaretto. Age and authenticity

 
While age of the stone itself cannot be gauged by radiocarbon dating, the Florida lab team tested samples of the patina -  layers of natural build-up on the surface of undisturbed rock. Finding carbon-containing material, they performed radiocarbon testing and produced a time estimate of 2,250 (plus or minus 40) years ago. Calibrating the results put the date sometime between 390 and 200 B.C. The experts deduced that the carbon had come from wood that grew and was burned around that period, which would mean the inscription on the tablet had been produced earlier.
 
Enter Israel's Antiquities Authority, which formed two separate teams of experts. Working on a voluntary basis, they tested the tablet with nearly every method known to archaeology to determine its authenticity. Dr. Elisabetta Boaretto, who heads the Radiocarbon Dating lab at the Weizmann Institute, was asked to evaluate the results of the Florida radiocarbon dating.
 
To help answer the question: "Is it authentic?" she had to ask: "Could it have been faked?"
 
While the results of the lab tests were not in doubt, several other aspects of the testing led her to question the relation between the radiocarbon date of the charcoal and the authenticity of the tablet inscription. For one thing, the patina contained several materials, including clay and charcoal. Boaretto suspected that the Florida lab may have dated them together. And because the C14 in clay comes from organic matter that could have mixed with the clay at any time, its presence could have skewed the results.
 
More worrying, however, was the fact that no one could say exactly where the tablet had been found or by whom. In a proper archaeological dig, radiocarbon dating goes hand in hand with analyzing the context in which the artifact is found -  the chronology of the layers above and below and the age of other artifacts in the same layer. Dating would be considered conclusive only when all the evidence matched. In the case of the Jehoash tablet, there was only a bit of charcoal to go by.
 
And yet, in spite of the irregularities, the charcoal is clearly very old. In explanation, Boaretto points to the radiocarbon lab, where labeled cardboard boxes containing all kinds of artifacts, including charcoal, sit on open shelves. "A person who knows some archaeology could easily come to the lab, express interest, and even request a little of this or that."
 
Her conclusion was that the radiocarbon dating did not prove the age of the tablet or its authenticity. The rest of the team also came up with results that were at odds with what should have been found had the tablet been truly ancient. The second team formed by the Antiquities Authority to examine the writing on the tablet also reached the same conclusion. Thus the "Jehoash tablet" was declared a fake.
 
Scientific Archaeology
English
Yes

In Sync with the Sun

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The great 18th-century botanist Carl Linnaeus is said to have planted a 'timekeeping' garden in which he could tell the hours of the day by the opening and closing of various flowers. Like Linnaeus' flowers, most plants and animals have internal biological clocks called 'circadian rhythms,' which synchronize daily activities such as awakening or petal spreading.
 
Prof. Meir Edelman of the Plant Sciences Department, working with Dr. Autar Mattoo of the USDA Agricultural Research Service in Maryland, has recently found that a 24-hour circadian clock regulates the most basic function in plants -  photosynthesis (the process in which plants produce sugar and oxygen -  see box).
 
Edelman and Mattoo have been collaborating on studies of photosynthesis for over 20 years, ever since Mattoo arrived at Edelman's lab from India for a two- year stint as a guest researcher. Since that time, their research has focused on an unusual protein central to photosynthesis.

 

Prof. Meir Edelman. Daily rhythm
 
The protein, called D1, sits right at the heart of the plant's energy centers, and is the dynamo of the photosynthetic process. Edelman and Mattoo were intrigued by their finding that a phosphate molecule regularly binds to, and is later released from, D1. They demonstrated that this process (called phosphorylation) does not occur at a steady rate; rather, its magnitude rises and falls in a 24-hour cycle. This swing between peak and ebb met all of the criteria for circadian rhythms: It continued for several days even when night and day cycles were artificially interrupted in the lab, and the cycle could be reset -  just as the body of a person traveling across different time zones resets its sleep cycle after a few days. (The cycle did break down, however, when plants were kept in total darkness, as photosynthesis cannot take place without light.)
 
Interestingly, they saw that the high point of this cycle did not coincide with the time of peak sunlight. Instead, phosphorylation climaxed at about 10 a.m., several hours before high noon, and afterward began to drop off sharply. This meshed in with the scientists' belief that D1 acts as a 'light meter' for the plant's energy centers. The scientists theorize that the phosphorylation cycle may be timed to help plants protect themselves against a sunlight 'overdose': Although the plant depends on sunlight for nourishment, too much sunlight can damage plant cells. D1 is tuned to work in a wide range of light conditions, including the weak light of early morning and cloudy days. But when the intensity of the light passes a certain level, the system has more incoming energy than it can handle. To prevent overload, the plants must suppress the reaction.
 
Continuing their research into the mystery of circadian rhythmic control of the D1 protein, Edelman and Mattoo have isolated an enzyme they suspect may be the main agent of daily D1 phosphorylation. Now they are performing further experiments using this enzyme to see if it is, indeed, the mainspring of the photosynthesis clock.

Illustration: plants In Sync with the Sun

From sunlight to sugar

Photosynthesis is the process in which green plants and certain other organisms produce carbohydrates using light, water and carbon dioxide. The green pigment in plants (chlorophyll) collects energy from sunlight.

 
The plant then uses the sunlight to split water into hydrogen and oxygen. The oxygen is released to the atmosphere as a byproduct, while the hydrogen adheres to molecules of carbon dioxide that the plant has soaked up from the air, producing sugar. D1, the protein studied by Edelman, plays a central role in this process, using the collected energy to split water.
 
 
Prof. Edelman's research was supported by the Avron-Wilstaetter Minerva Center for Research in Photosynthesis. He is the incumbent of the Sir Siegmund Warburg Chair of Agricultural Molecular Biology.
 
 
Illustration: plants In Sync with the Sun
Environment
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Higher Yields, Lower Pollution

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Like miniature samurai, some species of fungi carry around an arsenal of personal weapons for use in overcoming assaults against the plants they are sworn to protect. Plants, like prosperous lords, grow faster and more luxuriantly when a member of the fungus genus Trichoderma is nearby. The fungal weapons, which include the biological, chemical and conventional, have made this group of fungi a favorite agent of biological plant disease control over the last decade.
 
Many fungi are known to attack plants. However, Trichoderma curiously sides with the plants, raising the possibility of "fighting fungus with fungus" instead of using pesticides (which are dangerous to humans and harmful to the environment).
 
Found in soil all over the world, Trichoderma is known to latch on to harmful fungi that attack plants and destroy them. By using specialized tools, Trichoderma coils around the body of the invading fungus and penetrates its outer cell walls using several enzymes, including potent chitin-eating enzymes called chitinases. (Chitin is the hard material found in the shells of beetles and crabs as well as in the cell walls of most fungi.)
 
Work in the lab of Prof. Ilan Chet, President of the Weizmann Institute, focuses on this important fungus and the chitinase genes that make it such a powerhouse of plant defense. Chet began his work on Trichoderma at the Hebrew University of Jerusalem, where he discovered two out of five versions of chitinase known to exist in Trichoderma. Each version is encoded by a different gene; and each gene is programmed to switch on in response to a different set of stimuli.
 
Today, at the Weizmann Institute's Biological Chemistry Department, he has isolated and sequenced a previously unknown gene responsible for producing a key chitinase enzyme, in research performed with team member Dr. Ada Viterbo, Prof. Aviv Zilberstein and Dr. Smadar Penini of Tel Aviv University, as well as scientists from the Hebrew University's Faculty of Agriculture. Chet's team then set out to determine what it takes to "turn on" the gene -  that is, produce the enzyme.
 

Remote sensing

 
The strongest stimulus they found for firing up chitinase production came from the presence of chitin in the cell walls of nearby, harmful fungi. This particular chitinase gene begins producing its cell-wall-eating enzyme even before there is physical contact between Trichoderma and the attacking fungus. The gene appears to use a remote sensing mechanism that detects foreign chitin by picking up on tiny molecules that the attacking fungus releases into the surrounding medium.
 
Other stresses, such as low levels of available nutrients and temperature extremes, can also trigger chitinase production.
 
The team also showed that when chitanase works in tandem with other, similar enzymes, a synergistic effect ensues, providing augmented firepower against invaders.
 

Early warning system

 
Trichoderma not only acts as a biocontrol agent -  it also functions as an extra helping of fertilizer. In the latest research to come out of the Weizmann Institute Trichoderma lab, Chet and postdoctoral fellows Michal Shoresh and Iris Yedidya have shown why this happens.
 
Trichoderma works its way through the outer layers of the plant's root tissue and into the spaces between cells, where it remains without injuring the plant. The researchers found that the plant responds by activating a part of its immune system. It thus seems that Trichoderma acts as a kind of "early warning" system, putting the plant on high alert and improving its readiness to deal with an actual attack. Plants hosting Trichoderma had quicker response times to onslaughts of harmful bacteria in any part of the plant and were able to defeat the invading microbes more easily. Because Trichoderma-inoculated plants are better equipped to ward off infection, they are free to devote more of their energy to growth.
 
The researchers noted a number of chemical changes in the leaves, indicating that signals are relayed systematically up the plant from the roots, triggering a coordinated chain of responses on the way. By analyzing the pattern of chemical changes, they determined that a specific defense mechanism, known as "induced systemic resistance," had been activated in the plant.
 
Once the weapons used by Trichoderma are understood, the knowledge can be applied in several ways. Current disease control methods that employ the fungus can be improved. In addition, the genes that carry the instructions for the weapons' manufacture are now being engineered for other organisms -  such as bacteria grown specifically for assorted pesticide applications or plants that will carry the disease resistance traits themselves.
 

A slow release

 
Friendly bacteria or fungi used in biocontrol agents are especially susceptible to the sun's ultraviolet rays and can also be destroyed by micro-organisms in the soil. Prof. Ilan Chet, together with Prof. Amos Nussinovitch of the Hebrew University's Faculty of Agriculture and doctoral student Cheinat Zohar-Perez, recently developed a "time-release" system that keeps the helpful microorganisms safe while allowing steady amounts of their disease-fighting enzymes to reach the plants.
 
In a trial conducted in cucumber plants, the spread of disease dropped by 80 percent. The system is based on the creation of tiny beads, some no more than a few microns in size,which are made from a water soluble polymer. Inside each bead, the scientists trap roughly a billion friendly bacteria or fungal spores along with enough nutrients to sustain them over time. Thus, the bacteria and fungal spores are able to continue producing enzymes that attack various disease-causing microorganisms.
 
The ecologically safe, biodegradable polymer breaks down over time, slowly releasing the microorganisms into the soil.
Options for producing the beads on a commercial basis are currently being explored.
 

Got the greenhouse blues

 
Greenhouses are ideal breeding grounds for many kinds of plant diseases, including fungal infections. High humidity and other greenhouse conditions contribute to the problem. Chemical applications are problematic, as workers are constantly exposed to the air and soil, and the chemicals often break down more slowly in the closed greenhouses. In addition, some fungal infections do not respond to known chemical pesticides, while others become resistant to particular chemicals over time.
 
For these reasons, biocontrol products, such as Trichoderma-based preparations, have made important inroads into the greenhouse market, especially for growers raising vulnerable seedlings. Thanks to Chet and his years of work on Trichoderma, Israel is a world leader in research and development of these products.
 
Outside the greenhouse, the demand is mounting for biological control methods as awareness of the risks of pesticides to consumers and the environment grows. For instance, production of one widely used chemical for control of fungal disease in soil, methyl bromide, will be banned world-wide in 2005 under the Rio Convention because it destroys the ozone layer. Therefore, developing resistant plants and creating biocontrol applications that can be used efficiently on all kinds of field crops are of the utmost importance.
 
Prof. Chet's research was supported by Myrna Strelinger, Tucson, AZ.
Environment
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After the Big Bang

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Kozlov, Fraenkel, Tserruya, Ravinovich and Cherlin. PHENIX rising

In the first millionth of a second after the Big Bang, atoms as we know them today did not yet exist.

 

The jets of blazing matter that dispersed in all directions in those first few fractions of a second contained a mixture of infinitesimal particles (quarks and gluons), called the quark-gluon plasma. This was the first form of matter in the universe. Later on, when the universe cooled down a bit and became less dense, the quarks and gluons organized into various combinations, forming particles such as protons and neutrons. Since then, in fact, quarks and gluons have not existed as free particles in the universe.

 

Scientists have been trying to recreate the quark-gluon plasma in the lab in a joint experiment including 460 physicists from 57 research institutions in 12 countries. Recent results strongly indicate that they they are on the right track.

 

The ongoing project, called PHENIX, is being conducted at the Brookhaven National Laboratory in Long Island, using an accelerator, called RHIC (Relativistic Heavy Ion Collider), built especially for creating the quark-gluon plasma. The Israeli team is led by Prof. Itzhak Tserruya, head of the Weizmann Institute's Particle Physics Department. Tserruya and his colleagues designed and built special particle detectors, called pad chambers, which are a central part of PHENIX's detecting system.

 

The accelerator creates two beams of gold ions and accelerates them toward each other, causing a head-on collision. The power of the collision (about 40 trillion electron volts, the highest level of energy attainable in the lab) turns part of the beams' kinetic energy into heat, while the other part turns into various particles. The first stage in the creation of these new particles, like the first stage in the creation of matter in the Big Bang, is assumed to consist of the quark-gluon plasma.

 

Quark gluon plasma condenses

 

 

Prof. Tserruya's research was supported by the Nella and Leon Benoziyo Center for High Energy Physics. He is the incumbent of the Samuel Sebba Professorial Chair of Pure and Applied Physics.

One of the ways to identify the quark-gluon plasma is by observing its interaction with other particles. When a single quark moves through regular matter, it emits radiation that slows down its progress somewhat. When it enters a very dense medium like quark-gluon plasma, its progress is slowed much more. That's precisely the phenomenon that has recently been observed and analyzed in the PHENIX project. According to physicists taking part in the experiment, these findings are very encouraging and could indicate that they have succeeded in creating the quark-gluon plasma.

 

Other than Tserruya, the Weizmann team participating in the PHENIX experiment included Prof. Zeev Fraenkel, Dr. Ilia Ravinovich, postdoctoral fellow Dr. Wei Xie and graduate students Alexandre Kozlov, Alexander Milov and Alexander Cherlin.

 
(l-r) Graduate student Alexandre Kozlov, Prof. Zeev Fraenkel, Prof. Itzhak Tserruya, Dr. Ilia Ravinovich, and graduate student Alexander Cherlin. An international experiment
Space & Physics
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Greenhouse Gas Might Green Up the Desert

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Prof. Dan Yakir. On carbon dioxide's trail

Missing: around 7 billion tons of carbon dioxide (CO2), the main greenhouse gas charged with global warming.
 
Every year, industry releases about 22 billion tons of carbon dioxide into the atmosphere. And each year, when scientists measure the rise of carbon dioxide in the atmosphere, it doesn't add up -  about half goes missing. Figuring in the amount that could be soaked up by oceans, some 5.5 billion tons still remain unaccounted for.
 
Now, a Weizmann study conducted at the edge of Israel's Negev Desert has come up with what might be a piece of the puzzle. A group of scientists headed by Prof. Dan Yakir of the Environmental Sciences and Energy Research Department found that the Yatir forest, planted at the edge of the desert 36 years ago, is expanding at an unexpected rate. The findings, published in Global Change Biology, suggest that forests in other parts of the globe could also be expanding into arid lands, absorbing carbon dioxide in the process.
 
The Negev research station is the most arid site in a worldwide network (FluxNet) established by scientists to investigate carbon dioxide absorption by plants.
 
The Weizmann team found, to its surprise, that the Yatir forest is a substantial "sink" (CO2-absorbing site): Its absorbing efficiency is similar to that of many of its counterparts in more fertile lands. These results were puzzling since forests in dry regions are thought to develop very slowly, if at all, and thus are not expected to soak up much carbon dioxide. (The more slowly a forest develops the less carbon dioxide it needs, since carbon dioxide drives the production of sugars, the plants' source of energy.) Yet the Yatir forest was growing at a surprisingly quick pace.
 
Why would a forest grow so well on arid land, counter to all expectations? ("It wouldn't have even been planted there had scientists been consulted," says Yakir.) The answer, the team suggests, might be found in the way plants address one of their eternal dilemmas. Plants need carbon dioxide for photosynthesis, which leads to the production of sugars. But to obtain it, they must open pores in their leaves and consequently lose large quantities of water to evaporation. The plant must decide which it needs more: water or carbon dioxide. Yakir suggests that the 30 percent increase of atmospheric carbon dioxide since the start of the industrial revolution eases the plant's dilemma. Under such conditions, the plant doesn't have to fully open its pores for carbon dioxide to seep in - a relatively small opening is sufficient. Consequently, less water escapes the plant's pores. This efficient water preservation technique keeps moisture in the ground, allowing forests to grow in areas that previously were too dry.
 
The scientists hope the study will help identify new arable lands and counter desertification trends in vulnerable regions.
 
The findings could provide insights into the "missing carbon dioxide" riddle, uncovering an unexpected type of sink. Tracking down such sinks could help scientists better assess how long such absorption might continue. It could also lead to the development of efficient methods for taking up carbon dioxide, possibly mitigating global warming trends.
 

Research in the forest

 

The Yatir forest was planted by the Jewish National Fund.
 
Prof. Yakir's research was supported by the Philip M. Klutznick Research Fund; the Avron-Wilstaetter Minerva Center for Research in Photosynthesis; the Minerva Stiftung Gesellschaft fuer die Forschung m.b.H; the Estate of the late Jeannette Salomons, the Netherlands; and the Sussman Family Center for the Study of Environmental Sciences.
Prof. Dan Yakir. On carbon dioxide's trail
Environment
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Teaching Computers to See

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Basri, Galun, Brandt and Sharon. Seeing is believing

 

Skeptic: Billions of nerve cells in the human brain are involved in the process of vision. Since scientists find it difficult to understand even one of those cells, it's inconceivable that computers will ever be able to see.

 

Scientist: All the more reason to start working on it.

 
If one could make a computer see, reproducing the natural visual process, one would be adding an important dimension to many aspects of life: Computers could lend an 'extra eye' in the operating room, alerting doctors to problems; surveillance systems would be greatly improved; and quality control in production lines could be significantly enhanced. Along the way, we might attain crucial insights into how the brain constructs images.
 
The problem is the way computers read images. They see them as grids whose tiny squares (pixels) each give the computer only one type of information: color. Color, though, can be an ambiguous guide when it comes to distinguishing between objects. A yellow butterfly on a yellow flower could be mistaken by the computer for part of the flower. A clown, displaying numerous colors, could be interpreted as many different objects. A zebra, having two alternating colors, could be split into the number of its stripes.
 
Recently, a team from the Weizmann Institute devised a method that significantly improves computers' ability to see. The new approach goes from the bottom up -  beginning with one pixel. Each pixel in the image is compared to surrounding pixels in terms of color. As groups of pixels emerge, they are compared to one another using a wide range of more complex parameters: texture (the zebra's alternating black and white stripes emerge as a 'texture' characterizing one object), shape (groups of pixels, in contrast to individual pixels, will form a shape), average fluctuations in color, and more.
 
Groups having common parameters are joined. The bigger the groups, the more the parameters can be made refined and complex. The different objects in the image are separated according to the combination of parameters, which are so diverse that the error range is very small.
 
It doesn't sound as though any of this can be done in the blink of an eye, but in fact this method is much faster than all other existing methods. The reason: In the first stages, when individual or small groups of pixels are compared, only a few 'simple' parameters are employed to compare them. At later stages, many more complex parameters are used to compare large groups of pixels, but by then there are much fewer groups to compare. Thus the complex parameters are also not as time consuming as might be expected.
 
The technique was developed by then Ph.D. student Eitan Sharon under the supervision of Profs. Achi Brandt and Ronen Basri and in collaboration with Dr. Meirav Galun, all in the Applied Mathematics and Computer Science Department. They are currently working to improve the approach.
 
Of course, even if a computer is finally able to distinguish easily between objects, other obstacles will have to be overcome before it is able to 'see' as we do. For one thing, it will have to be taught to interpret what it sees and to correctly categorize objects (for instance, to understand that a poodle and a German shepherd both belong in the 'dog' category despite their different appearances). Thanks to the complexity of our brains, we perform these functions easily. Will scientists find a way to simplify these functions so that they can be incorporated into computers? It may take a while until we find out.

Comparison: Original, Weizmann and other techniques

 

 

Prof. Brandt's research was supported by the Karl E. Gauss Minerva Center for Scientific Computation. He is the incumbent of the Elaine and Bram Goldsmith Professorial Chair of Applied Mathematics.

Prof. Basri conducts his research in the Moross Laboratory for Vision Research and Robotics.

Comparison: Original, Weizmann and other techniques
Math & Computer Science
English

Malaria's Achilles' Heel

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Years of basic research into how crystals form have now proven relevant to probing the anti-malarial properties of common drugs.

 

Malaria is a leading killer. While mostly confined to sub-Saharan Africa, regions in Asia, and Central and South America, it infects an estimated 300 to 500 million people every year and kills between one and three million, most of them children under the age of five.

 

The new study, conducted by Dr. Ronit Buller and Prof. Leiserowitz of the Institute's Materials and Interfaces Department, as well as Dr. Matthew Peterson and Dr. Orn Almarsson of Boston-based Transform Pharmaceuticals Inc., has uncovered the precise mechanism by which common anti-malarial drugs zero in on their parasitic target. Like most living organisms, malaria parasites require amino acids and iron. They obtain them by penetrating the host's red blood cells, where they munch on the readily available hemoglobin (see box). The problem is that one of the byproducts of hemoglobin breakdown -  heme -  is toxic to the parasite. The parasite overcomes this by chemically modifying the heme and neatly packaging it into non-toxic crystals called hemozoin.

Prof. Leslie Leiserowitz. Drug action

 

Anti-malarial quinoline drugs function by inhibiting the growth of the hemozoin crystals, causing heme to accumulate in toxic amounts that ultimately kill the parasite. Although numerous studies have focused on this interaction, the crystal's micron-sized dimensions and poorly shaped surfaces impeded all efforts to determine the drug's precise mechanism of action.

 

Ronit Buller, at the time completing her doctorate at the Institute, came upon a key article by researchers who had succeeded in determining the structure of the hemozoin crystal, yet they too were unable to show how the drugs inhibit crystal growth. "She realized that this was an ideal project for our lab," says Leiserowitz. "The challenge also excited me for a personal reason -  I grew up in South Africa, where for years I witnessed firsthand the effect of quinine on my father, who took the drug on his work trips to the jungles of Central Africa."

 

 

Binding site revealed

 

Using computer software to calculate the shape of the hemozoin crystal, the team was able to identify the crystal's fastest-growing faces. One of these faces had a corrugated shape with a "tailored," nearly lock-and-key fit for docking quinoline drugs. The team then demonstrated that these drugs bind strongly to this face, inhibiting crystal growth.

 

Having unraveled the crystal's shape and its target binding site, the researchers were able to show why certain malarial drugs are more effective than others. Moreover, their study, published in Crystal Growth and Design, has provided a blueprint for designing improved drug therapies. One central idea is to increase the number of binding sites between the target crystal and each drug.

 

Commenting on the study, Dr. Robert Rubin of Harvard Medical School remarked: "Over the last decade, malaria has reemerged as one of the most widespread infectious diseases due to its resistance to the quinoline drug family. These findings are critical in providing us with better information on current drugs and the emerging resistance to them, as well as offering help in developing new drugs."

 

OUTSMARTING THE IMMUNE PATROL

 

The difficulty in combating the malaria parasite lies in its constantly changing form, which keeps it one step ahead of the human immune system. When an infected mosquito bites a human, it introduces the parasite, which spends only 30 minutes on average in the bloodstream before penetrating the liver – hardly enough time for the body to mount an effective antibody response. Once in the liver, each parasite invades a separate cell and begins to divide, producing thousands of parasites. The body’s immune T cells go to work at this point, but their response takes around 10 to 12 days, while the parasites are way ahead, taking only a week before they burst out of each liver cell, destroying it in the process. They then quickly invade red blood cells (which are not protected by killer T cells), where they start to break down the cell’s hemoglobin, gobbling up its amino acids. They continue to invade new cells and multiply furiously, resulting in millions of parasites.

Dr. Ronit Buller. Inspired by an article

 

Prof. Leiserowitz's research was supported by the Helen & Milton A. Kimmelman Center for Biomolecular Structure & Assembly; and the Joseph and Ceil Mazer Center for Structural Biology.

 

 
Prof. Leslie Leiserowitz
Chemistry
English

A Time to Remember, A Time to Forget

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Prof. Yadin Dudai (center) with graduate students. Importance of forgetting

While some people try to remember, others try unsuccessfully to forget. People whose memories have a debilitating effect, such as trauma sufferers who remain haunted by their experience throughout their lives, would benefit from the ability to intentionally dim or erase specific memories without affecting the others.

 

A step toward reaching this goal has recently been made by a Weizmann team. The scientists have uncovered a fundamental rule governing the workings of the brain. The findings were recently published in Science.

 

Every memory that we acquire undergoes a "ripening" process (called "consolidation"), which lasts a few hours after the memory is formed. During this time, certain treatments can erase that memory. Until recently, the accepted belief was that every memory consolidates just once, and after that the window of opportunity for erasing that memory closes.

 

However, recent evidence has shown that calling up a memory might again make it susceptible to disruption. If true, it might be possible to activate a "memory eraser" immediately after the act of remembering, even though years may have passed since the original memory was formed.

 

Yet leading labs in the world, spurred on by that evidence, came up with seemingly contradictory results: Working with animals, they found that only in some cases did it appear possible to erase old memories upon recall.

 

The current findings, made by Prof. Yadin Dudai of the Neurobiology Department, explain the puzzling discrepancies in the previous findings and shed light on how memories are recalled and stabilized.

 

Winner loses all

 

To understand the findings, think of the bits of information stored in our memories. Each may have many associations, some conflicting with others. For instance, a certain food can arouse memories of taste -  delicious or disagreeable; a person can be remembered in pleasant or unpleasant contexts, and so on. When we next taste the food or see the person, all of the associated memories are evoked. But in the end, only one of them will determine our reaction (i.e., become dominant). This memory dictates whether we will eat the food or reject it, whether we will smile at our acquaintance or ignore him. Dudai's team, which included Mark Eisenberg, Tali Kobilo and Diego Berman, found that only the memory that won the competition for dominance became sensitive to erasure. It is this memory that must be consolidated once again before being reinstalled in long-term memory. In other words, the winner, under the appropriate circumstances, loses all. In Dudai's words, "The stability of the recalled memory is inversely correlated with its dominance."

 

We can make you forget

Dudai's team carried out the study with rats and fish. The rats learned to remember flavors; the fish learned to remember flashes of light. In both instances, the animals were trained to associate the stimuli with conflicting memories (the light, for instance, would signal danger only some of the time). In both species, researchers showed that the dominant memory was the only one that could be erased by administering an appropriate drug within a few minutes of recall.

 

Studies on humans have not yet been conducted, but Dudai points out that the closer we get to the basic principles of memory, the more similarities exist among animals, including humans. Thus drugs found to be effective in eliminating memories in animals may work in humans as well, offering a much awaited piece of good news to trauma sufferers.

 

DEFINING MEMORY

 

Dudai's recently published book, Memory from A to Z, provides a unique and valuable introduction to the field of memory for students and researchers alike. It consists of over 130 entries, bound within a coherent conceptual framework. Each entry starts with a definition, or set of definitions, followed by an in-depth and provocative discussion of the origin, meaning, usage and applicability of ideas and problems central to the science of memory and scientific culture at large. The entries provide a versatile tool kit as a source of definitions, information and further reading, as well as a trigger for contemplation, discussion and experimentation. The book can serve as a useful aid to study, teaching and debates, as well as a trigger for future experimentation.

 

Prof. Dudai's research was supported over the years by the Abe and Kathryn Selsky Foundation; the Nella and Leon Benoziyo Center for Neurosciences; the Lester Crown Brain Research Fund; the Abramson Family Brain Research Program; the Carl and Michaela Einhorn-Dominic Brain Research Institute; and the Murray H. & Meyer Grodetsky Center for Research of Higher Brain Functions. He is the incumbent of the Sara and Michael Sela Professorial Chair of Neurobiology.

Memory from A to Z, Prof. Yadin Dudai, Oxford University Press, 331 pp.

 
Prof. Yadin Dudai (center) with graduate students Mark Eisenberg and Tali Kobilo. Learning to forget
Life Sciences
English

Blood Test for Smokers

English

Prof. Zvi Livneh and his research team. Low enzyme activity

 

Lung cancer is one of the most deadly malignancies, responsible for 30 percent of all cancer deaths. Most sufferers from the disease – about 90 percent – are smokers. Weizmann research has now yielded a new blood test that can detect smokers who are at especially high risk of developing the cancer.

 

Our DNA is damaged about 20,000 times a day by such factors as sunlight, smoke and reactions within the body. If left unrepaired, damaged DNA can lead to cancer. Fortunately, the body has a stock of enzymes whose function is to repair DNA. Upon detecting the damage, the enzymes "operate" on the DNA, replacing the damaged parts with new ones. The efficiency of these repair enzymes is thus critical for preventing cancer.

 

After years of research into DNA repair systems, Prof. Zvi Livneh and Dr. Tamar Paz-Elizur of the Biological Chemistry Department decided to concentrate on a specific DNA repair enzyme called OGG1 (8-oxoguanine DNA glycosylase 1). This repair enzyme deletes DNA parts damaged by toxic molecules (called oxygen radicals) found in tobacco smoke. By developing a new blood test that enables them to measure the level of OGG1 activity, the researchers found that 40 percent of lung cancer patients have low levels of OGG1 activity. This, in contrast to only 4 percent of the general population. "Only 10 percent of heavy smokers develop lung cancer," says Livneh, "and that suggested to us the involvement of a personal genetic susceptibility." In collaboration with Dr. Meir Krupsky of the Chaim Sheba Medical Center in Tel Hashomer, the scientists tested this theory in lung cancer patients.

 

Smokers still have higher risk

 

The findings, published in the Journal of the National Cancer Institute, show that smokers who carry a genetic marker signifying low OGG1 activity are around 5-10 times more likely to get lung cancer than smokers whose OGG1 activity is normal – and 120 times more likely than non-smokers who have normal OGG1 activity. (Smoking increases the risk, since it results in more damage to the DNA, and thus more work for the repair enzymes.)

 

Screening smokers for low OGG1 activity will help them make more informed decisions about smoking. Of course, even smokers with normal OGG1 activity are at greater risk of getting lung cancer than the general population, and the blood test will not ensure that they don't get the disease. In addition, smoking causes other types of cancer and cardiovascular diseases, whose relation to OGG1 activity is still unknown.

 

The Weizmann team also included Dr. Sara Blumenstein and Dalia Elinger. Statistical analysis was conducted by Dr. Edna Schechtman from Ben-Gurion University of the Negev.

 

 

 

Prof. Livneh's research was supported by the M.D. Moross Institute for Cancer Research; the Dolfi and Lola Ebner Center for Biomedical Research; the Levine Institute of Applied Science; and the Josef Cohn Minerva center for Biomembrane Research. He is the incumbent ot the Maxwell Ellis Professorial Chair in biomedical Research.

 

LUNG CANCER STATS

According to the American Lung Association:

  •  Lung cancer is the leading cancer killer in both men and women.

 

  • There were an estimated 164,100 new cases of lung cancer and an estimated 156,900 deaths from lung cancer in the United States in 2000.

 

  •  In most cases, the disease might have been prevented - nearly 90 percent of lung cancer cases are caused by smoking.

 

  •  Secondhand smoking is responsible for approximately 3,000 lung cancer deaths and as many as 62,000 deaths from heart disease annually.

 

  • When a person quits smoking, the risk of lung cancer decreases each year. Ten years later, the risk drops to one-third to one-half the risk for smokers.

 

  •  In addition, quitting smoking greatly reduces the risk of developing other smoking-related maladies, such as heart disease, stroke, emphysema and chronic bronchitis.

 

  •  Radon is considered the second leading cause of lung cancer in the U.S. today, with 12 percent of all lung cancer deaths linked to radon. The EPA estimates that nearly one out of every 15 homes in the U.S. has indoor radon levels at or above the level at which homeowners should take action - 4 picocuries per liter of air (pCi/L) on a yearly average. Exposure to radon in combination with cigarette smoking greatly increases the risk of lung cancer.

 
Clockwise from bottom left: Dr. Meir Krupsky, Dalia Elinger, Dr. Edna Schechtman, Dr. Tamar Paz-Elizur, Dr. Sara Blumenstein, and Prof. Zvi Livneh. Calculated risks
Life Sciences
English

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