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Science Feature Articles</p>

Morphine Effect on Key Brain Mechanism Determined

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Prof. Rabi Simantov. Inhibited dopamine uptake
 

The chemistry of morphine addiction is being studied by Prof. Rabi Simantov of the Department of Molecular Genetics and Virology. Part of this research, recently published in Neurosciences Letters, may shed light on the addictive properties of a wide range of other substances, including alcohol, amphetamines, cocaine and nicotine.


The euphoria accompanying addiction to morphine and various other drugs results from excessive activity on the part of dopamine -- a neurotransmitter that relays impulses between nerve cells in the brain. Ordinarily, dopamine signals are turned off when the neurotransmitter is absorbed by a neuron; any inhibition of this process leads to excessive signaling. Prof. Simantov has now shown that chronic exposure to morphine inhibits dopamine uptake via a previously unrecognized mechanism.

In animal studies, morphine addiction was found to reduce the number of nerve-cell transporters that normally absorb dopamine and turn off its signals.

Prof. Simantov also showed that this reduction of transporters takes place only in the anterior basal forebrain -- the region containing drug "reinforcement and reward pathways." Since these pathways are strongly associated with the brain activity responsible for euphoria and analgesia -- phenomena induced by substances as varied as alcohol, amphetamines, cocaine and nicotine -- the addiction mechanism triggered by morphine is likely to be involved in the brain's response to these substances as well. The findings, therefore, might provide a basis for new strategies aimed at reducing dependency on some or all of these habit-forming drugs.
 
The study was supported, in part, by the Anti-Drug Authority of Israel, and the Office of the Chief Scientist in the Israeli Ministry of Health. Prof. Simantov holds the André Lwoff Chair of Neurogenetics.
 
Life Sciences
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DNA "Repair Enzymes" Tricked into Producing Mutations

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Prof. Zvi Livneh and Orna Cohen-Fix. Alternative mutation pathway
 

Vital "repair enzymes" responsible for preventing genetic mutations are at times hoodwinked into causing such mutations themselves, according to a recently published Institute study. It is known that environmental stress factors such as ultraviolet light or certain chemicals may create lesions on DNA strands, preventing the DNA molecule from issuing clear instructions on how to form an identical replica of itself. Were it not for the "rescue" operations of special "repair enzymes" -- proteins that search for lesions, cut them away and replace them with healthy DNA material -- mutations would be formed in uncontrollable fashion. However, Prof. Zvi Livneh and doctoral student Orna Cohen-Fix of the Department of Biochemistry have now found that these same enzymes can be duped into producing the very mutations they are designed to avert.


"Our hypothesis," says Prof. Livneh, "is that this occurs when two different lesions face one another on complementary DNA strands." The restoration procedure starts out normally, with the repair enzyme excising one of the lesions. "Then however," says Livneh, "the enzyme encounters an unexpected situation. The reserve store of information on the opposite strand, which it uses in order to fill in the gap, turns out to be faulty as well. A point of no return has been reached in the process, and the enzymatic machinery is left with no choice other than to proceed with the repair operation and to duplicate the defective material -- thereby producing a mutation."

This newly discovered process appears to be an "alternative" mutation pathway. In the more commonly recognized mechanisms, ordinarily dormant proteins called bypass factors help the DNA copying machinery to progress through lesions, thus generating permanent mutations in the cell's genetic material.

Livneh and Cohen-Fix used an original model system in which ultraviolet (UV) light-induced genetic changes are produced in test tubes by a protein extract from the bacterium Escherichia coli. The planned adaptation of this model to UV-exposed mammalian cells will allow the investigation of such dual pathways in mammalian systems, including those of humans.

Support for this work has been provided by the U.S.-Israel Binational Science Foundation and the Minerva Foundation, Munich, Germany.

Schematic diagram of lesion entering DNA duplicating machinery

 

Space & Physics
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Mathematicians Attempt to Design More Human-Like Robots

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2-D snapshots help in 3-D recognition

Institute mathematicians have made major strides in the continuing quest to transfer elements of human intelligence -- particularly vision and control of arm-movements -- to robots.

One of the main difficulties in endowing robots with "vision" is teaching them to recognize three-dimensional objects, which can be observed from an infinite number of viewing angles. In an approach developed by Prof. Shimon Ullman and Dr. Ronen Basri, a 3-D object is represented by a handful of 2-D snapshots. A set of mathematical calculations is then used to combine the snapshots that best coincide with novel views from any desired angle.

This method has recently been successfully tested on computer models by Basri and Dr. Ehud Rivlin, who plan to try it on actual robots by storing in their memory 2-D pictures of a room containing contours of various objects, such as furniture and wall paintings. The robot, equipped with a camera, would then determine its location in the room, or reach a designated target, by taking pictures of various surrounding objects and then matching them against the contour bank in its memory.

In related work, Dr. Shimon Edelman collaborating with Prof. Heinrich Bulthoff of the Max Planck Institute for Biological Cybernetics, has shown that the human brain itself may recognize 3-D objects in this very fashion ? by comparing its 2-D image to a series of memorized "snapshots" of previously seen objects. The scientists have provided evidence that recognition takes place when the rain, through interpolation, selects the "snapshots" that most closely approximate the new object.

Prof. Tamar Flash focuses not on vision but on the brain's control of arm movements. She combines laboratory measurements with various modeling techniques to characterize the arm motions of healthy people. Furthermore ? together with Dr. Rivka Inzelberg of the Tel Aviv Medical Center and Prof. Amos Korczyn of this Center and of Tel Aviv University ? Flash studies the movements of people suffering from Parkinson's disease and other neurological disorders in order to pinpoint how they differ from the norm. Her research is also aimed at developing advanced motion control and planning schemes for robotic arms.
 

Profs. Ullman and Flash, Drs. Basri and Edelman

 
 
Math & Computer Science
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Self-Tinting Coating for Plastic Lenses Developed

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Kringayuz and his team. Better tinting material

Self-tinting eyeglasses with plastic lenses may soon be significantly improved thanks to a new material developed by Institute scientists. The material, a polymer that darkens when exposed to sun, can be used to create an ultrathin coating on plastic lenses.

Self-tinting spectacles have been around for a while (with up to 10 million pairs being sold annually in the U.S. alone). However, until recently, they could only be made of glass, while about 80 percent of people in industrial countries who wear prescription eyeglasses prefer lightweight plastic lenses.

Even though self-tinting plastic lenses have also become available of late, they are slow to change color and their effectiveness steadily weakens with time. In addition, once their tinting ability is lost, it cannot be restored.

These drawbacks stem from the fact that the photochromic material ? the active substance that changes color when exposed to light ? is dissolved into the plastic. The amount of the photochrome that can be incorporated into the lens in this manner is limited, and its tinting capacity is affected by the properties of the plastic.

Prof. Valeri Krongauz, who pioneered photochromic polymers 20 years ago, developed the new material together with Organic Chemistry Department colleagues Alexander Zelichenok, Frida Buchholtz, Dr. Shlomo Yitzchaik, Professor Emeritus Ernst Fischer and Dr. Judith Ratner. It has been shown to overcome these problems in laboratory tests.

This polymer contains high concentrations of a chemically bound photochromic substance. As a result, a layer only several microns thick has powerful tinting ability. The polymer darkens quickly when exposed to sunlight and immediately clears indoors.

A thin film of the photochromic polymer can be applied to the surface of any plastic lens, according to Prof. Krongauz. He said such film may eventually be easily removed or reapplied in an optometrist's office, such like certain scratch resistant layers are now restored.

A patent application for its production has been filed by the Yeda Research & Development Co., which is responsible for the commercial application of Weizmann research.
 
Chemistry
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New Water Softener Provides Alternative to Ion Exchange

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Prof. Kedem Ben-Dror. Soft water without salt

Novel water-softening equipment based on Institute technology is being manufactured by EcoSoft, a new company in the Kiryat Weizmann Industrial Park, adjacent to the campus. This equipment is designed to soften water without polluting underground aquifers with salt.

Established by Crecor B.V. of the Netherlands and Israeli paint manufacturer Tambour Ltd., EcoSoft will exploit the innovative "cake" filtration method for water softening developed by Weizmann Institute's Prof. Ora Kedem and EcoSoft's Jonathan Ben-Dror.

Many industries, laundries, hotels, municipal waterworks and private households soften their water by removing calcium salts in order to reduce the need for detergents and prevent the scaling of pipes and heating elements.

At present, the most commonly used method of removing calcium is ion exchange, in which the mineral is extracted in purifying columns that are regenerated for future use with the help of salty water. Yet this seemingly clean process leads to invisible pollution caused by the dumping of tons of sodium-rich effluent, which finds its way into the aquifers. Therefore, pressure has been mounting throughout the world to ban the ion-exchange method.

Ion exchange was introduced to replace the age-old method of lime softening, which consists of adding lime to hard water so as to cause precipitation of calcium carbonate. However, lime softening is hardly used today because it requires vast ponds to allow the precipitate to settle, takes about 24 hours and creates enormous pools of sludge.

The new cake filtration method is based on similar chemistry: caustic soda solution is added to hard water in order to induce the precipitation of calcium carbonate. However, the passage of the alkaline water -- supersaturated with calcium carbonate -- through a filter cake leads to complete precipitation within seconds. Rapid crystal growth and formation of new crystals produce a readily disposable, and even useful precipitate instead of sludge.

The installations required for cake filtration are only one-tenth the size of those needed for lime softening.

Cake filtration technology was patented by the Yeda Research & Development Co., which facilitates commercial exploitation of Institute research.

Prof. Ora Kedem of the Department of Membrane Research and Biophysics holds the M. Myer Cyker Chair of Membrane Research.
 
Chemistry
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Future Rainfall Changes may be Far Greater than Now Predicted

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Dead Sea caves hint at rainfall patterns

Future change in rainfall patterns may be far more sweeping than has been predicted by current models, according to an Institute study reported in Climatic Change. The study was conducted by the late Prof. Mordeckai Magaritz, who pioneered environmental research at the Weizmann Institute. It shows that significant fluctuations in rainfall levels have taken place over the last 7,000 years, and that they cannot be explained by existing climatic models. Changes in the future, therefore may be far greater than such models have forecasted.


Prof. Magaritz compared variations in precipitation over the past 7,000 years as reflected in four paleoclimatic records: 1. the advance and retreat of Alpine glaciers; 2. the width of salt-cave passages in Mt. Sodom, overlooking the Dead Sea; 3. oxygen isotope compositions of mollusk shells from the eastern Mediterranean; and 4. the size of Lake Chad in Africa. He found that throughout this period, large cyclical changes in precipitation occurred simultaneously in all these regions.

This cyclical pattern cannot be explained by existing climatic models, which are based almost exclusively on changes in factors such as the temperature and the concentration of gases in the atmosphere - elements believed to have remained relatively constant during the period under study. Moreover, major decreases in precipitation took place within spans of only several hundred years, whereas the atmospheric factors underlying climatic change models ordinarily require thousands of years to make a tangible impact.

The fact that natural variability in rainfall is much larger than expected also implies that it will be difficult to know whether future changes in precipitation are caused by human contamination of the atmosphere or by natural variations. Prof. Magaritz suggested designing precipitation models that will take into consideration interactions between systems with a short response time, such as the influence of the oceans on water in the atmosphere and the balance of heat between the two.

Prof. Magaritz, who was the incumbent of the Barry Rymer Chair for Environmental Research, passed away in September after a lengthy illness.
 

Prof. Mordeckai Margaritz. Confounding predictions

 
 
Environment
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Mysteries of Embryo Development Probed

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Profs. Geiger and Kam. A new view of embryonic development

 

Institute researchers have thrown new light on one of the greatest mysteries of biology - how intricate cellular mechanisms allow the fertilized egg, a single cell, to develop into a complex three-dimensional structure with trillions of cells that form various tissues and organs.


Genetically controlled mechanisms underlying the formation of organs in a developing embryo are studied by Profs. Benjamin Geiger and Zvi Kam of the Department of Chemical Immunology in collaboration with Dr. Anat Yarden and Sigal Bitzur. Their research model is the zebrafish, whose nearly transparent embryos complete crucial developmental steps in less than a day. The scientists focus on several families of genes, particularly those leading to the production of adhesion molecules involved in the assembly of individual cells into tissues and organs.

In order to observe organ formation in a live embryo, the researchers have designed a novel microscopic system that follows the development and movement of embryonic cells. The complex data are processed in a powerful computer, producing a digital multidimensional image. The result is a time-lapse recording that captures the 20 hours during which a fertilized egg develops into a partially formed embryo with tens of thousands of cells.

In applying this new approach to the study of cell adhesion molecules, the scientists have shown that these proteins, present on the surfaces of cells, serve a dual function. While long known to hold cells together, recent Weizmann results indicate that they also help to recruit signal transduction molecules that trigger processes such as cell growth and differentiation. The adhesion sites thus serve as miniature "communication centers" affecting cell behavior and fate.

A disruption of these complex mechanisms in either embryos or mature organisms can lead to disease. For example, the mechanism of contact inhibition, which instructs cells to stop growing when they reach a certain density in tissues, is lost in cancer cells. Consequently, an understanding of the way contact signals are transmitted into cells may eventually aid researchers to develop effective new means of suppressing tumor growth.

Prof. Geiger holds the Erwin Neter Chair of Tumor Biology and Prof. Kam, the Israel Pollak Chair of Biophysics.
 
Development in a day
 
 
Life Sciences
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Mechanism of Blood Pressure Regulation Clarified

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Prof. Garty and Dr. Asher. Sodium ion flow

A "dual action" control system that enables sodium channels to play a vital role in maintaining normal blood pressure has been discovered by Prof. Haim Garty, Dr. Carol Asher and co-workers at the Institute's Department of Membrane Research and Biophysics. Since abnormalities in this mechanism are a major cause of hypertension, the research may lead to more effective drugs for this disorder.

Salt -- in the form of sodium and chloride ions -- is transported into the blood through special channels located in the inner linings of the kidney, colon and urinary bladder. If too much salt enters the circulatory system, water follows in its wake, resulting in high blood pressure. Thus the body possesses a sophisticated mechanism for regulating the flow of sodium ion -- a task performed mainly by the steroid hormone aldosterone. Prof. Garty's group has now discovered a "dual action" process underlying aldosterone-sodium channel interaction.

The researchers injected frog oocytes, the germ cells contained in ovaries, with RNA isolated from toad tissue incubated in the presence of aldosterone. Short incubation periods doubled the channel activity without producing new channel RNA, whereas long incubation periods not only stepped up the activity in the existing channels but also triggered the manufacture of new ones. In a corroboratory study with Prof. Nathan Dascal of the Sackler School of Medicine at Tel Aviv University, RNA extracted from intestinal tissues of chickens that were fed a low-salt diet readily produced channels in frog oocytes, while no channel activity was detected in oocytes injected with RNA isolated from chickens given a high-salt diet. Both studies indicate that the enhancement of channel performance is controlled by a mechanism different from the one that induces the manufacture of new channels.

Certain anti-hypertensive drugs, such as diuretic amiloride, combat high blood pressure by blocking sodium transport through the channels. However, these drugs are not highly specific and produce side effects. Prof. Garty is now attempting to clone the sodium channel and identify its amiloride binding site -- key steps in the design of more potent and specific drugs to combat high blood pressure.
 
Keeping blood pressure even
Life Sciences
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More Nutritious Potatoes Produced

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Dr. Galili and genetically engineered potato plant

A potato richer in amino acids essential to the body has been genetically engineered by Dr. Gad Galili, Ms. Orit Shaul and Dr. Avihai Perl of the Department of Plant Genetics.

A major nutritional drawback of many crop plants -- including grains, potatoes and legumes -- is their low content of lysine and several other crucial amino acids. The level of these important organic compounds remains low mainly because the plant automatically curtails their production as soon as they begin to accumulate. Using potato and tobacco plants as experimental models, Dr. Galili has found a way to overcome this problem.

The accumulation of amino acids in plants inhibits the activity of dihydrodipicolinate synthase (DHPS), one of the enzymes that synthesize lysine. Looking for a more resistant enzyme, Dr. Galili and associates turned to the DHPS in E. Coli bacteria, which is far less sensitive to lysine build-up. He extracted DNA segments coding for the bacterial DHPS, engineered them to enable their expression in plants, and introduced them into potato and tobacco cells. In both of these species, lysine levels manufactured by the genetically engineered enzyme proved to be significantly higher than those produced by the natural variety. Tobacco plants exhibited up to a 15-fold increase in free lysine, while in potato plants it increased four-fold in the leaves, five-fold in the roots and three-fold in the tubers.

Human proteins contain about 20 different kinds of amino acids, the basic building blocks of all protein. However ten of these -- the "essential" amino acids -- cannot be synthesized by the body and must be provided ready-made via the diet. Malnutrition, especially among children, is prevalent in many poor parts of the world where the standard diet contains insufficient quantities of these vital compounds, and cultivable potatoes richer in essential amino acids would help alleviate this situation.

Dr. Galili's current research is also aimed at improving the incorporation of lysine into seed proteins of cereals, thereby elevating lysine levels even further in these important crop plants; such an advance would greatly enhance the prospects for the development of more nutritious varieties of cereals.
Environment
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New Method for 'Improving' Light Signals

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Prof. Kurizki. Light signals

A simple scheme for the generation and detection of "noiseless" light signals may some day improve the efficiency of information transfer via optical signal processor, computers and other high-tech devices. The theoretical basis for this novel method was developed by Prof. Gershon Kurizki and Ph.D. student Boris Sherman of the Institute's Department of Chemical Physics; parts of the study were carried out with Prof. Peter Knight and his group at Imperial College, London.

Light signals used in optical communications and computing carry minute bits of information, detected by measuring the number of photons (elementary packets of light energy) they contain. Such measurements, however, are imprecise because light signals originating even from the best lasers are inevitably distorted by "noise" due to random fluctuations in the number of photons produced. The Weizmann Institute and Imperial College researchers have suggested new strategies to reduce such "noise."

They propose the coupling of laser light output to a special storage cavity exposed to a beam of atomic particles that interacts with the light. The idea is to select those atoms that are unchanged by the cavity, which implies that the light trapped inside has a fixed number of photons, and is therefore free of "noise."

One technique involves passage of the atoms in close proximity to tiny plastic or glass spheres on which surface photons are trapped. Another possibility is the passage of atoms through a regularly spaced array of such spheres, which enables atoms to emit light in a single direction only. The new schemes are expected to be tested experimentally in the near future.
Space & Physics
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