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Science Feature Articles</p>

Shedding Light on Infertility

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Dr. Boris Tartakovsky. Preventing miscarriage

A Weizmann Institute scientist has shown that the injection of certain natural growth factors into pregnant mice helps prevent them from miscarrying. Dr. Boris Tartakovsky of the Institute's Department of Chemical Immunology found two growth factors, or cytokines, that dramatically reduce miscarriages among mice that are naturally prone to abort, as well as among normal mice injected with an abortion-inducing substance.

The findings may help shed light on the cause of many unexplained cases of repeated miscarriages and infertility among women. It is also hoped that the research could eventually lead to techniques for improving the success rate of in-vitro or test-tube pregnancies.

These studies are an outgrowth of Dr. Tartakovsky's earlier work which led to the discovery of a particular cytokine, CSF-1, that impairs fertility in mice. Since some cytokines block the action of others, Tartakovsky sought to identify growth factors that might possibly promote pregnancy. He eventually found two: tumor necrosis factor-alpha (TNF-a) a pro-inflammatory substance produced by many tissues, and granulocyte macrophage colony stimulating factor (GM-CSF), a promoter of white blood cell production.

Tartakovsky's experiments showed that the abortion-inducing effects of CSF-1 could be largely overcome by parallel injections with pregnancy-promoter GM-CSF. He also demonstrated that TNF-a dramatically reduced miscarriages in a strain of mice highly prone to spontaneous abortions. Moreover, CSF-1-induced embryo damage was found to occur before embryo implantation, and correcting this effect must be attempted at an early phase if the embryo is to be salvaged.

This latter finding could have implications in human test-tube embryo implantation and may suggest a possible strategy for improving the low success rate (about 20%) associated with this procedure.

Dr. Tartakovsky holds the Pauline Recanati Career Development Chair in Immunology.
 

Embryo at implantation stage

Life Sciences
English

Innovative Research May Improve Composite Materials

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Microscopic crystal structure in plastic

A new Institute study of how neighboring fibers in composite materials interact under stress may contribute to an improvement of everything from bowling lanes and bicycle frames to auto parts and spacecraft.

More and more modern conveniences make use of composite materials, in which some type of reinforcement -- usually in the form of thin fibers (typically 10 microns in diameter) -- is embedded into a matrix, most often polymeric. The composites are designed to exhibit properties that are superior to those of their individual components.

A critical factor in the performance of these materials is their response to stress. In order to assess the interaction of various fibers under conditions of stress, Prof. Daniel Wagner of the Department of Materials and Interfaces created a unique model microcomposite containing a small number of fibers that could be placed at varying distances from one another by means of precise micropositioning equipment. By applying stress to the system and monitoring the progress of the resultant breaks in the fibers, Wagner found that when the fibers were closer together, the breaks in one fiber were specifically correlated with those in its neighbors. This finding enabled him to formulate a "stress concentration factor" showing the amount of load that is transmitted from one fiber to its neighbors when a break occurs. Such information may lead to a more efficient positioning of fibers within a matrix and to a better understanding of fracture physics in such materials.

In a related study, Prof. Wagner is investigating how crystal formation affects the interface between a fiber and a thermoplastic melt. When the melt is cooled down quickly to a constant temperature, crystals are formed at the interface and grow perpendicularly to the fiber -- a phenomenon that, if better understood, may some day be exploited to improve the properties of thermoplastic composites.

Prof. Wagner -- a recent recipient of the prestigious Fiber Society Award for Distinguished Achievement -- has been invited to join an international effort geared to probing composite interfaces, sponsored by the French Office National d'Etudes et de Recherches Aerospatiales and the British Royal Aerospace Establishment. His research is funded in part by the United States-Israel Binational Science Foundation.
 

Prof. Daniel Wagner. Investigating composites

 
 
Chemistry
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Cutting Custom-Designed Diamonds

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Star of David diamond. Laser shapes

Improved methods developed by Institute Prof. Yehiam Prior for sawing diamonds with lasers may lead to the eventual automation of the entire industry and to routine production of unusually shaped, custom-designed diamonds. The advance overcomes a key obstacle that has until now prevented lasers from being employed more extensively in diamond processing.

Despite their speed and flexibility, lasers are today used only as a last resort on diamonds that cannot be sawed by conventional, mechanical means because of the larger percentage loss of the stone's weight. However, the improved methods developed by Prof. Prior of the Chemical Physics Department have reduced that loss by more than half, making laser sawing, in many cases, comparable to the mechanical process.

In addition to being extremely fast, lasers can be used to cut diamonds into virtually any shape, irrespective of the orientation of the stone's underlying crystalline structure. This allows the cutter to obtain the largest possible gem from a raw stone and to design unusual shapes, such as a Star of David. With mechanical sawing, the direction of sawing is limited by the natural crystal axes of the stone.

Prof. Prior is also collaborating with other Israeli researchers in a study that may ultimately lead to the development of a diamond-processing industry based totally on lasers and computer-aided design. The idea, he explains, is to make available the technology whereby a person can "computer design" a diamond and transfer this information to a laser that would cut and shape the raw stone.

Prof. Prior, whose research is funded by the Israel Diamond Institute, holds the Sherman Chair of Physical Chemistry.
 
Chemistry
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New Uses for Veteran Accelerators

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Weizmann Institute accelerators have been long used to explore the properties of atomic nuclei, but now they also contribute to the solution of a variety of medical, ecological, and other problems. Many of these projects are directed by investigators from other research institutions.

Prof. Michael Paul of the Hebrew University, for example, utilizes the Koffler Accelerator of the Canada Centre of Nuclear Physics as an extremely sensitive mass spectrometer in order to follow the movement of man-made isotope calcium - 41 in the body. His investigations promote an understanding of the bone-weakening disease, osteoporosis. Paul and colleagues are also tracing the environmental impact of nuclear energy exploitation by determining variations in radioisotope iodine-129 (a by-product of modern nuclear fission reactors) in ice cores from Greenland. Another group, including Dr. Yeshayahu Lifshitz of Israel's Nahal Soreq Nuclear Research Center and Prof. Michael Hass of the Institute's Nuclear Physics Department, uses the Pelletron to simulate the radiation of outer space. This enables study of the reliability of electronic chips used in satellites.

Prof. Jacob Klein and his group of the Institute's Department of Materials and Interfaces are working on the 3 MV Van de Graaff accelerator. Their investigation of nuclear reactions in polymers sheds light on how the chemical structure and size of individual polymer molecules provide information on the physics of polymeric materials, including their stability, thin-film structure, and transport properties.

The Institute's third accelerator, the EN Tandem, is used by a Tel Aviv University group to develop Israel's first free-electron laser (FEL), the most powerful type of laser known to science. FELs may eventually be a key component in the production of environmentally clean energy via magnetic confinement nuclear fusion.

Fundamental research continues at the Pelletron Accelerator. Profs. Cyril Broude and Michael Hass of the Nuclear Physics Department are probing the shapes, magnetism, and other properties of nuclei. These determinations help provide a better understanding of the forces operating between their component protons and neutrons. Another group, headed by Professors Zeev Vager (Nuclear Physics Department) and Ron Naaman (Chemical Physics Department), is applying its own novel method, involving both lasers and Coulomb explosion imaging, to determine the structure of molecular species, work important for verifying theoretical models of molecular structure.

Prof. Klein holds the Herman F. Mark Chair of Polymer Physics; Prof. Naaman, the Aryeh and Mintzi Katzman Chair; and Prof. Vager, the Isidor I. Rabi Chair of Physics.
Space & Physics
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The Goal: Early Diagnosis of High-Risk Fetuses

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Keeping the fetus healthy

 

Identification of fetuses likely to suffer from future neurodevelopmental problems due to placental malfunction may become possible as early as four to six weeks after conception, thanks to a new technique developed by Weizmann Institute scientists and physicians from the Tel Aviv Medical Center. Based on a simple urine analysis, the new method should markedly facilitate the prevention or mitigation of postnatal complications such as infant death or mental retardation.


Prof. Ephraim Yavin of the Institute's Neurobiology Department and Prof. Shaul Harel of the Tel Aviv Medical Center and Tel Aviv University have studied the link between "ischemic," or blood-deprived fetuses and intrauterine growth retardation (IUGR), which occurs in 3% to 10% of all pregnancies and is responsible for 33% of all low birthweight infants. IUGR -- often recognized at birth by large head circumference relative to body weight --is common among low-income populations, smokers and certain ethnic groups and families. Although up to 30% of IUGR infants "catch up" to normal children within a few years, the disorder is linked to infant and early childhood mortality, cerebral palsy, speech and learning disabilities and small body size.


IUGR often arises from circulatory problems in the expectant mother, which cause a temporary disturbance in the flow of oxygen and glucose to the developing fetal brain. If oxygen supply returns quickly enough, damage can be kept within a recoverable range; however Yavin and Harel found that partial restoration of oxygen-rich blood causes the cerebral blood elements and the placenta to produce lipid-derived hormones called protaglandins. One of them, thromboxane, acts to constrict the blood vessels -- decreasing blood supply to the brain and exacerbating the ischemic damage -- while the other, prostacyclin, serves to dilate the vessels, thereby reducing the damage. By measuring the ratio of these two compounds in blood and urine samples of a pregnant woman, it should be possible to determine the danger of her baby suffering from developmental retardation.

Currently, ischemic fetuses are identified through Doppler ultrasound measurements of blood flow from mother to fetus and from the fetal heart to the fetal brain. These measurements become reliable only after 18-20 weeks of pregnancy. It is believed that Yavin's and Harel's new method could be used as early as 4-6 weeks into pregnancy.

This research is supported by the Gulton Foundation, NY, Fidia s.p.a., Italy, and the Revson Foundation of the Israel Academy of Science and Humanities.
 
Life Sciences
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Biological Sensors Devised by Institute Scientists

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Dr. Itzhak Yuli. Detecting drugs or explosives

 

A novel design for highly sensitive biosensors -- microelectronic devices that take advantage of biological detection and amplification mechanisms -- has been developed by Prof. Carlos Gitler and Dr. Itzhak Yuli of the Institute's Department of Membrane Research and Biophysics. Such biosensors may some day be used instead of animals to detect drugs and explosives, or to test pharmaceuticals and cosmetics. They may also be integrated into portable on-line monitors to greatly improve the sensitivity of standard chemical analysis performed in medical diagnostics, and eventually may be inserted into the human body to continuously monitor minute concentrations of chemicals relevant to various diseases.


Biological sensory systems are known to be nature's most efficient and highly selective detection devices. The environmental signals that living organisms detect through vision, smell or taste, and the internal signs involved in nerve triggering or hormonal stimuli, all produce changes in chemical states. Some of these chemical modulations activate a variety of ion channels -- proteins that by opening up create pathways for the flow of electrically charged elements through otherwise highly impermeable cell membranes.

The new biosensor design is based on an artificial biological membrane containing synthetic varieties of such ion channels, sophisticatedly attached to a gold electrode. These channels open up in response to specific chemical signals, causing modifications in the electrical conductivity of the membrane, which can be easily recorded.

The new bionic device will use a liquid crystalline phospholipid membrane that is indirectly attached to the gold electrode by "spacer arms" of detergent-like molecules. One end of these rod-like molecules blends naturally into the membrane, while the other end is modified so as to acquire a high affinity for gold. This design endows the membrane with both mechanical stability and structural flexibility, and minimizes the need to utilize an ultrasmooth electrode surface.

Sensing elements of two different types are under study. One of them involves synthetic polypeptides resembling melittin, a toxin in bee venom which spontaneously penetrates into cell membranes to form active ion channels. A second system uses genetically engineered proteins similar to natural ion channels that open upon recognizing a given substance.

Title to the patent on this biosensor design is held by Yeda Research & Development Co. Ltd., which promotes the commercial exploitation of know-how originating in the Weizmann Institute.

Prof. Gitler holds the E. Stanley Enlund Chair in Membrane Research.
 

Artificial membrane and ion channel

 
 
Space & Physics
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Two Proteins with Therapeutic Potential Discovered

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Urinary proteins stop excess hormone production
 

A natural immune-system hormone implicated in vascular failure occurring in septic shock and cerebral malaria can be neutralized by two urine proteins recently discovered at the Institute. Furthermore, since the hormone may contribute to tissue damage accompanying autoimmune disorders, graft rejection and graft-versus-host disease, the proteins may be effective against these disabilities as well.


The hormone in question, known as "tumor necrosis factor" (TNF), is formed by white blood cells in response to injury or infection. However, TNF production can become excessive, leading to the destruction not only of substances foreign to the body but also of healthy tissues, thus inducing the onset of various diseases. Prof. David Wallach of the Institute's Department of Membrane Research and Biophysics, along with Ph.D. student Harmut Engelmann (M.D.) and Dr. Dan Aderka of Ichilov Hospital, discovered two urinary proteins called TBPI and TBPII (TNF-binding proteins I and Ii) that inhibit TNF activity.

The purification and amino acid sequencing of the TBPs was carried out by the group of Prof. Wallach in collaboration with Institute researchers Prof. Menachem Rubinstein, Dr. Dalia Rotman and Dr. Daniella Novick. Based on the sequencing, Prof. Wallach and doctoral students Yaron Nophar, Oliver Kemper and Cord Brakebosch cloned the genes for these proteins. Analysis of the gene structure revealed a close evolutionary relationship between the TBPs and segments of known hormone receptors.

Patents for the TBPs and their genes have been registered by Yeda Research & Development Co. Ltd., and recombinant TBP is already being synthesized by an Israeli company, InterPharm. Preclinical trials have shown that natural and recombinant forms of the protein, in microgram amounts, effectively protect against septic shock in mice. Clinical trials in humans are expected soon.

Prof. Rubinstein holds the Edna and Maurice Weiss Chair of Interferon Research.
 
Life Sciences
English

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