(l-r) Standing: Dr. Haim Weissman, Dr. Boris Rybtchinski, Elisha Krieg. Sitting: Dr. Eyal Shimoni and Elijah Shirman. Flexible bonds
Chemistry based on molecular interactions in water could yield novel materials that stand up to pressure but are much more adaptive than those created with traditional methods. Dr. Boris Rybtchinski and his team in the Institute’s Organic Chemistry Department (Faculty of Chemistry) recently applied this original approach to produce a unique nanoparticle filter that not only simplifies the size-sorting process but also comes apart for cleaning and is recyclable. Their findings appeared in Nature Nanotechnology.
Almost all functional materials produced today are held together by strong, irreversible bonds known as covalent bonds. These bonds are what make such materials as polymers strong, but under normal circumstances they lack the ability to change, making them difficult to recycle or even dispose properly. In contrast, so-called supramolecular systems are held together by noncovalent interactions. Supramolecular systems are easily self-assembled and are adaptive – they can be self-healing, for instance – so they are easy to fabricate and recycle. Until now, however, what these systems gained in flexibility, they lost in strength.
Rybtchinski and his team, including Ph.D. students Elisha Krieg and Elijah Shirman, and staff scientists Drs. Haim Weissman and Eyal Shimoni, have been looking at a noncovalent attachment between molecules known as hydrophobic bonding. Hydrophobic molecules are “water-hating”: When placed in water they bond together, something like coalescing oil droplets. An analysis of the chemical forces reveals that hydrophobic bonds could be relatively strong yet adaptive, not to mention environmentally friendly and cost-efficient. But are these bonds sturdy enough for producing useful new materials that can compete with the existing covalent ones?
Supramolecular systems are good candidates for such specialized applications as nanoparticle filters. Existing filters – made to retrieve particles just a few billionths of a meter across – are expensive and difficult to use, and they tend to clog and break. A recyclable filter – one whose bonds break and reform – could overcome these problems.
The researchers created molecules with a large hydrophobic component and poured a water solution of them onto standard, inexpensive filter material with very large pores. Instead of running through the filter, the molecules bonded into a sponge-like three-dimensional network filled with even, nanometer-sized spaces.
The network turned out to be an excellent nanoparticle filter. When the scientists passed a solution containing gold nanoparticles through the nanoscale network, only those smaller than five nanometers (a critical size for many applications) progressed beyond the supramolecular membrane. To retrieve the nanoparticles and reuse the filter, the team simply dissolved the filter’s hydrophobic bonds with common alcohol. Repeating the process over and over, they found that the filter network could be easily dissolved and reconstituted for further rounds of sorting – without any loss of performance or efficiency.
Next the scientists wanted to see if their network could be even more specific in sorting the particles. This time they created a slightly thicker 3-D structure. After pouring the nanoparticle solution through, they inspected the network under the Institute’s electron microscope. As anticipated, the smaller particles had penetrated farther into the material while the larger ones were caught closer to the surface, and these could easily be separated according to size – enabling very precise sorting.
Rybtchinski believes that, with a few adjustments, recyclable filtering networks could eventually present a more efficient, greener alternative to some of the particle-sorting methods used today. The methodology may also be promising for separating such biomolecules as proteins and DNA. “This method could be quite cost-efficient and easy to use. There is practically no waste involved. Best of all, we have demonstrated a completely new application for non-covalent bonds: We’ve shown they can be robust and at the same time easily reversible, enabling novel noncovalent materials that are more versatile and environmentally friendly than their covalent counterparts.”
Yeda, the Institute’s technology transfer arm, has filed for a patent for the noncovalent membranes.
Dr. Boris Rybtchinski’s research is supported by the Yeda-Sela Center for Basic Research; and Yossie Hollander, Israel. Dr. Rybtchinski is the incumbent of the Abraham and Jennie Fialkow Career Development Chair.
Long-term memory is a slippery thing. Just how slippery was demonstrated a few years ago by Weizmann Institute scientists, who erased entire memories in rats just by blocking a certain protein in the brain. In other words, memory – even the part we imagine to contain neatly packed files – is in reality a dynamic piece of equipment that must be actively maintained to work. Now these scientists have shown, in research that appeared in Science, that manipulating that same protein can enhance memory.
The protein – PKMzeta – is produced in the brain in response to learning, and it acts on the synapses – the active contact points between neurons. It continues to operate there long after the memory has been formed, suggesting that its function is tied not to learning (that is, absorbing information) but to keeping what is learned available in the long-term memory. In 2007, Prof. Yadin Dudai and research student Reut Shema of the Neurobiology Department, together with Prof. Todd Sacktor of SUNY Downstate Medical Center, New York, trained rats to avoid a specific taste and then blocked the activity of PKMzeta in their brains. While the control rats still had a strong aversion to the taste even months after the training, those in which the activity of the protein was briefly blocked had no such qualms, appearing to have forgotten what they had learned.
Overexpression of PKMzeta in the insular cortex. A merged picture of a neuron stained with GFP (green), PKMzeta (blue), and NeuN (red)
But could extra doses of PKMzeta actually improve memory? Investigating this claim turned out to be a more difficult prospect than blocking protein activity. Simply injecting the protein into the rats’ grey matter was not an option, as the brain is built to keep such extraneous material from reaching the neurons. So Dudai, Shema and Sacktor teamed up with Dr. Alon Chen and Sharon Haramati, also of the Neurobiology Department, to create harmless viruses that carry extra copies of the PKMzeta gene into the brain cells’ nucleus, tricking the neurons themselves into producing greater quantities of the protein.
Once again, they trained the rats to avoid the taste. Weeks after the training, the rats whose brains were churning out more of the protein were much more likely to avoid the taste. In other words, an excess of PKMzeta effectively enhanced their memories. This is the very first demonstration that memories formed long ago can be augmented by manipulating a component of the memory machinery in the brain.
While the technique they developed is suitable only for the lab, the researchers hope that by shedding light on the function of this key component of the memory machinery their findings might eventually point to ways of preventing or treating memory loss. Shema: “Our research is evidence that the brain is very plastic – even long-term memories can be augmented.”
Prof. Yadin Dudai's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Abe and Kathryn Selsky Memorial Research Project; Miel de Botton Aynsley, UK; Dr. Henry Kaminer, New York, NY; Marla L. Schaefer, New York, NY; and Lisa Mierins Smith, Canada. Prof. Dudai is the incumbent of the Sara and Michael Sela Professorial Chair of Neurobiology.
Dr. Alon Chen's research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Irwin Green Alzheimer's Research Fund; the Mark Besen and the Pratt Foundation, Australia; Roberto and Renata Ruhman, Brazil; and Martine Turcotte, Canada. Dr. Chen is the incumbent of the Philip Harris and Gerald Ronson Career Development Chair.
When we suddenly get the answer to a riddle or understand the solution to a problem, we can practically feel the light bulb click on in our head. But what happens after the “Aha!” moment? Why do the things we learn through sudden insight tend to stick in our memory?
“Much of memory research involves repetitive, rote learning,” says Kelly Ludmer, a research student in the group of Prof. Yadin Dudai of the Institute’s Neurobiology Department, “but in fact, we regularly absorb large blocks of information in the blink of an eye and remember things quite well from single events. Insight is an example of a one-time event that is often well-preserved in memory.”
To investigate how lessons we gain from insight get embedded in our long-term memory, Ludmer, Dudai and Prof. Nava Rubin of New York University designed a test with “camouflage images” – photographs that had been systematically degraded until they resembled inkblots. When volunteers first viewed the images, they were hard-pressed to identify them. But after the camouflage switched with the original, undoctored picture for a second, the subjects experienced an “Aha!” moment – the image now popped out clearly even in the degraded photograph. Their perceptions, says Ludmer, underwent a sudden change – just as a flash of insight instantly shifts our world view. To tax their memory of the insightful moment, participants were asked to repeat the exercise with dozens of different images and, in a later, repeat session, they were given only the camouflaged images (together with some they hadn’t seen before) to identify.
Aha! Mouse over "camouflage" image for undoctored picture
The team found that some of the memories disappeared over time, but the ones that made it past a week were likely to remain. All in all, about half of all the learned “insights” seemed to be consolidated in the subjects’ memories.
To reveal what occurs in the brain at the moment of insight, the initial viewing session was conducted in a functional MRI (fMRI) scanner. When the scientists looked at the fMRI results, they were surprised to find that among the areas that lit up in the scans – those known to be involved in object recognition, for instance – was the amygdala. The amygdala is more famously known as the seat of emotion in the brain. Though it has recently been found to play a role in the consolidation of certain memories, studies have implied that it does so by attaching special weight to emotion-laden events. But the images used in the experiment – hot-air balloons, dogs, people looking through binoculars, etc. – were hardly the sort to elicit an emotional response. Yet not only was the amygdala lighting up in the fMRI, the team found that its activity was actually predictive of the subject’s ability to identify the degraded image long after that moment of induced insight in which it was first recognized.
“Our results demonstrate, for the first time, that the amygdala is important for creating long-term memories – not only when the information learned is explicitly emotional, but also when there is a sudden reorganization of information in our brain, for example, involving a sudden shift in perception,” says Ludmer. “It might somehow evaluate the event, ‘deciding’ whether it is significant and therefore worthy of preservation.”
Prof. Yadin Dudai's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Abe and Kathryn Selsky Memorial Research Project; Miel de Botton Aynsley, UK; Dr. Henry Kaminer, New York, NY; Marla L. Schaefer, New York, NY; and Lisa Mierins Smith, Canada. Prof. Dudai is the incumbent of the Sara and Michael Sela Professorial Chair of Neurobiology.
(l-r) Ari Tadmor, Prof. Nava Dekel and Dr. Ketty Shkolnik. Active ingredient
Antioxidants are sold over the counter everywhere. They’re added to food, drink and even face cream. But according to Prof. Nava Dekel of the Biological Regulation Department, we still don’t have a complete understanding of how they act in our bodies. New research by Dekel and her team, recently published in the Proceedings of the National Academy of Sciences, USA, (PNAS), has revealed a possible unexpected side effect of antioxidants: They might cause fertility problems in females.
Common antioxidants include vitamins C and E. These work by eliminating molecules called reactive oxygen species that are produced naturally in the body. Stress can cause these chemically active molecules to be overproduced, and in large amounts they damage cells indiscriminately. By neutralizing these potentially harmful substances, antioxidants may, theoretically, improve health and slow down the aging process.
But when Dekel and her research team, including her former and present Ph.D. students Dr. Ketty Shkolnik and Ari Tadmor, applied antioxidants to the ovaries of female mice, the results were surprising: ovulation levels dropped precipitously. That is, very few eggs were released from the ovarian follicles to reach the site of fertilization, compared to those in untreated ovaries.
Pregnant Venus. The other side of stress molecules
To understand what lies behind these initial findings, the team asked whether it is possible that the process of ovulation might rely on the very “harmful” substances destroyed by antioxidants – reactive oxygen species.
Further testing in mice showed that this is, indeed, the case. In one experiment, for instance, Dekel and her team treated some ovarian follicles with luteinizing hormone, the physiological trigger for ovulation, and others with hydrogen peroxide, a reactive oxygen species. The results showed hydrogen peroxide fully mimicked the effect of the ovulation-inducing hormone. This implies that reactive oxygen species that are produced in response to luteinizing hormone serve, in turn, as mediators for this physiological stimulus leading to ovulation.
Among other things, these results help fill in a picture of fertility and conception that has begun to emerge in recent years, in which it appears that these processes share a number of common mechanisms with inflammation. It makes sense, says Dekel, that substances which prevent inflammation in other parts of the body might also get in the way of normal ovulation, and so more caution should be exercised when administering such substances.
Much of Dekel’s research has focused on fertility – her previous results are already helping some women become pregnant. Ironically, the new study has implications for those seeking the opposite effect. Dekel: “On the one hand, these findings could prove useful to women who are having trouble getting pregnant. On the other, further studies might show that certain antioxidants might be an effective means of birth control that could be safer than today’s hormone-based prevention.”
Dekel and her team are now planning further studies to investigate the exact mechanics of this step in ovulation and to examine antioxidant effects on mice when administered in either food or drink. In addition, they plan to collect data on the possible link between females, antioxidant supplements and difficulty in conceiving.
Prof. Nava Dekel's research is supported by the M.D. Moross Institute for Cancer Research; the Y. Leon Benoziyo Institute for Molecular Medicine; the Jeanne and Joseph Nissim Foundation for Life Sciences Research; the Yeda-Sela Center for Basic Research; the Willner Family Center for Vascular Biology Head; the Dwek Family Biomedical Research Fund; the Phyllis and Joseph Gurwin Fund for Scientific Advancement; the J&R Foundation; la Fondation Raphael et Regina Levy; and Allyson Kaye, UK. Prof. Dekel is the incumbent of the Philip M. Klutznick Professorial
(l-r) Dr. Alon Chen, Gili Ezra-Nevo, Dr. Evan Elliott, Adi Neufeld Cohen and Dr. Michael Tsoory. Relieving stress
Stress and anxiety are normal: They evolved to help us deal with daily threats to our existence. But the stress response – pounding heart, tensed muscles, sweating palms – is meant to shut down after the threat has passed. People who have a hard time “turning off” their stress response, often as a result of psychological trauma, can develop post-traumatic stress syndrome, as well as anorexia, anxiety disorders or depression.
How does the body recover from its response to shock or acute stress? This question is at the heart of research conducted by Dr. Alon Chen of the Institute’s Neurobiology Department. The response begins in the brain, and Chen concentrates on a family of proteins that play a prominent role in regulating this mechanism. One protein in the family – CRF – is known to initiate a chain of events that occurs when we cope with pressure, and scientists have hypothesized that other members of the family are involved in shutting down that chain. In research that appeared in the Proceedings of the National Academy of Sciences (PNAS), Chen and his team have now, for the first time, provided sound evidence that three family members known as urocortin 1, 2 and 3 – are responsible for turning off the stress response.
The research group, including Adi Neufeld Cohen, Dr. Michael Tsoory, Dmitriy Getselter and Shosh Gil, created genetically engineered mice that don’t produce the three urocortin proteins. Before they were exposed to stress, these mice acted just like the control mice, showing no unusual anxiety. When the scientists stressed the mice, both groups reacted in the same way, showing clear signs of distress. Differences between the groups appeared only when they were checked 24 hours after the stressful episode: While the control mice had returned to their normal behavior, appearing to have recovered completely from the shock, the engineered mice were still showing the same levels of anxiety the scientists had observed immediately following their exposure to the stress.
Cultured nerve cells that have been inoculated with RNA-bearing viruses. This RNA targets the CRF stress response, reducing gene expression
Clearly, the urocortin proteins are crucial for returning the body to normal, but how, exactly, do they do this? To identify the mechanism for the proteins’ activity, Chen and his team tested both groups of mice for expression levels of a number of genes known to be involved in the stress response. They found that gene expression levels remained constant both during and after stress in the engineered mice. In contrast, patterns of gene expression in the control mice showed quite a bit of change 24 hours after the event. In other words, without the urocortin system, the “return to normal” program couldn’t be activated, and the stress genes continued to function.
Chen: “Our findings imply that the urocortin system plays a central role in regulating stress responses, and this may have implications for anxiety disorders, depression, anorexia and other conditions. The genetically engineered mice we created could be effective research models for these diseases.”
Dr. Alon Chen's research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Irwin Green Alzheimer's Research Fund; the Mark Besen and the Pratt Foundation, Australia; Roberto and Renata Ruhman, Brazil; and Martine Turcotte, Canada. Dr. Chen is the incumbent of the Philip Harris and Gerald Ronson Career Development Chair.
(l-r) Dr. Benjamin Friedrich, Prof. Samuel Safran, Dr. Yair Shokef and Elon Langbeheim. Looking underneath
Stem cells, like Goldilocks, need a bed that’s “just right” before they can turn into muscle. Too soft, and they become nerve or brain cells; too hard, and they turn to bone. A recent collaboration between scientists in Israel, the US and Germany revealed how the cells “feel” the bed’s hardness and why just the right amount of give in the bed’s “springs” sets them on the path to becoming muscle.
Several years ago, Prof. Dennis E. Discher at the University of Pennsylvania made a surprising discovery: He could direct a stem cell’s fate in the lab simply by adjusting the stiffness of its underlying substrate. A cell sitting on a soft surface not only took on a different shape than a cell on a rigid one; it showed expression of different sets of genes. Prof. Sam Safran of the Weizmann Institute’s Materials and Interfaces Department, in the Faculty of Chemistry, was intrigued by these results. He wanted to know what it is about stem cells that responds to such purely physical cues as substrate stiffness. Dr. Assaf Zemel, a former postdoctoral fellow in his group, now at the Hebrew University of Jerusalem, and Safran proposed a theory for how the substrate controls the alignment of “stress fibers” within the cell. Discher and his group, including Andre Brown and Dr. Florian Rehfeldt, tested the model experimentally.
The stress fibers are thin but strong strands of the protein actin. These can form a sort of flexible “skeleton” in the cell body, where they are often organized into webs or parallel bundles, endowing the cell with a loosely solid structure, similar in texture to toothpaste. But actin fibers are more than just rigging: They are linked by another molecule called myosin, which hooks onto two parallel actin filaments and uses the energy of the cell to pull on them. This induces a contractile force in the cell. Such “active springs” can be found in many types of cells, where they give rise to an intrinsic tension in the structure; they are also related to the mechanism that enables our muscles to contract.
Actin-myosin stress fibers
Safran and Zemel reasoned that a living cell, which tends to spread on certain surfaces, attempts to pull itself back by activating its contractile stress fibers. The balance between these two opposing tendencies lies in the relative stiffness of the cell and the substrate. It eventually affects the amount of tension in the cell and the development of the stress fibers themselves. The more rigid the substrate – that is, the less give there is – the harder the fibers pull back. As the stress fibers feel more tension, the physical effort generates a request for reinforcements, and the cell creates additional fibers.
The model predicted that when the amount of give is just right, the stress fibers in the cell will line up in bundles more or less parallel to the long axis of the cell. The experiments, carried out by Discher’s group on synthetic substrates that mimicked the hardness of the different materials encountered by various differentiating stem cells, bore this out. A paper describing the theory and the experimental findings recently appeared in Nature Physics.
When the substrate is too soft, the contracting fibers can easily overcome the cell’s stretching. As such a cell is fairly relaxed, it produces relatively few stress fibers, and these pull in no particular direction. When the substrate is stiffer, however, the shape of the cell comes into play. The spread-out stem cell tends to be more oval than round, giving rise to fibers that are longer in one direction. Since longer strands feel more stress than shorter ones, the additional stress fibers develop mainly along the cell’s elongated axis. “And this,” says Safran, “is exactly the arrangement needed to make muscle. Our muscles contract because the fibers all pull together in the same direction.”
If the rigidity of the substrate increases more than this, the fibers become so tense that the cell’s shape and direction cease to be relevant, and new fibers form in every direction.
This physical effect might reach even deeper into the cell, says Safran. Current research in this area is looking into the possibility that the stress fibers pull on the walls of the cell nucleus. In other words, the shape of the nucleus itself may be determined by substrate stiffness, and this could influence which genes are expressed as the cell continues to develop. In related research, together with Discher and his group, Safran and postdoctoral fellow Dr. Benjamin Friedrich are looking closely at how substrate hardness affects the development of the orderly bands of stress fibers found in muscles.
For Safran, this research has had an immediate impact: The close collaboration between the different groups has led a Weizmann graduate, Dr. Amnon Buxboim, to conduct postdoctoral research on stem cell physics in Discher’s lab in Pennsylvania, in collaboration with Safran and Friedrich at Weizmann. Interactions with Zemel in Jerusalem and Rehfeldt, now in Gottingen, Germany, are also ongoing. In the future, the insights from this research might be applied in biomedical research and biotechnology to direct cell and tissue development.
Prof. Samuel Safran’s research is supported by the Carolito Stiftung. Prof. Safran is the incumbent of the Fern and Manfred Steinfeld Professorial Chair.
(l-r) Drs. Eugene Katz, Ronit Popovitz-Biro and Maya Bar-Sadan, Profs. Daniel Feuermann, Reshef Tenne, Jeffrey Gordon and Moshe Levy, and Dr. Ana Albu-Yaron. Nanoparticles
Sunlight – valued as a nearly infinite source of energy – can also provide an unusual glimpse into the nanoworld. In a new study, led by researchers from the Weizmann Institute and Ben-Gurion University of the Negev, highly concentrated solar radiation helped reveal the shapes assumed by certain inorganic nanoparticles. This research, conducted in collaboration with German scientists, sheds new light, as it were, on the behavior of particles on the nanoscale and could lead to advanced uses for various nanomaterials.
Nearly two decades ago, the Weizmann Institute’s Prof. Reshef Tenne and his colleagues in the Chemistry Faculty were the first to discover that inorganic materials could form hollow, cage-like nanostructures. Until then, only carbon molecules were known to form hollow spheres, which came to be called fullerenes due to their likeness to the geodesic domes built by the architect Buckminster Fuller. Tenne’s discovery opened up a new field of research into the inorganic fullerene-like particles, creating exciting applications, including the manufacture of superior solid lubricants, and posing a host of new questions, particularly those concerning the connection between the particles’ superior properties and their structure and shape.
The “true” inorganic fullerene – the smallest, most stable cage-like particle of inorganic material – is shaped like an octahedron resembling an eight-sided die. Such tiny octahedra have already been produced at the Weizmann Institute and elsewhere. But larger inorganic fullerene-like structures have also been produced, these being multi-layer spheres. At what point, exactly, does the octahedron become spherical in shape?
An intermediate molybdenum disulfide nanoparticle has an octahedral center and a spherical outer shape
This is a crucial question – in part because the two shapes appeared to endow the nanoparticles with different properties – and it has been answered by the new study, published recently in the international edition of Angewandte Chemie. The international team worked with molybdenum disulfide (MoS2) nanoparticles just a few millionths of a meter across.
Their first goal was to create an atomic vapor of molybdenum disulfide. Laser light, used in previous nanoscale studies with this material, was found to produce only small octahedra made up of 20,000 atoms. To generate larger octahedra, Ben-Gurion University researchers headed by Prof. Jeffrey Gordon built an innovative table-top solar concentrator consisting of an elaborate system of mirrors that created an ultra-intense solar beam focused to a magnitude of about 15,000 suns. Inside a quartz capsule, molybdenum disulfide heated to 2,500oC was vaporized into a hot cloud of individual atoms. Since the concentrated solar beam is appreciably wider than the beams of typical pulsed lasers, the evaporated atoms could, upon cooling, form much larger clusters than those obtained with lasers.
Lead author of the study Dr. Ana Albu-Yaron of the Weizmann Institute and her colleagues used a series of electron microscopes – including the most advanced one in Dr. Lothar Houben’s laboratory at the Jülich Research Center in Germany – to view the architecture of these nanoparticles. The picture that emerged provided the first support for certain theoretical predictions in this area made by Prof. Gotthard Seifert’s group at the Technical University of Dresden, which turned out to be impressively accurate.
In addition to the distinct eight-sided and spherical shells, the team observed hybrid nanoparticles of molybdenum disulfide assuming an intermediate “transition” shape, and the study revealed precisely at which size each shape occurs. The smallest molecules, made up of no more than 100,000 atoms, were hollow octahedra. Larger particles, comprising about 500,000 atoms, had an intermediate structure: octahedral layers at the core, surrounded by multiple onion-like spherical shells.
Beyond addressing fundamental questions in materials science, these results can be of practical significance. Molybdenum disulfide is used as a catalyst for removing sulfur from fossil fuels to prevent acid rain. In the form of nanoparticles, the catalyst could be much more effective: Thanks to their voluminous, three-dimensional structure, such particles are likely to be more accessible to interaction with the sulfur, speeding up the removal process. The researchers plan to explore the potential of their solar-generated nanoparticles as catalysts once they manage to produce them in sufficient amounts. Such catalysts would be doubly beneficial to the environment: First, they are produced by a clean solar method; second, they promise to be more effective than existing ones at reducing the damage caused by fossil fuels.
Additional applications for the solar-synthesized fullerene-like particles might stem from the fact that the eight-sided molybdenum disulfide molecules are metallic in character whereas the spherical ones are semiconductors. The intermediate particles are hybrids: A metal-like component is embedded within a semiconductor, a structure that could find new uses in the semiconductor industry – for example, in the manufacture of advanced sensors.
The study was conducted by Dr. Ana Albu-Yaron and Prof. Moshe Levy in the lab of Prof. Reshef Tenne of the Weizmann Institute’s Materials and Interfaces Department, together with Dr. Ronit Popovitz-Biro of the Institute’s Chemical Research Support, and by Prof. Daniel Feuermann and Dr. Eugene A. Katz in the lab of Prof. Jeffrey Gordon at Ben-Gurion University, in collaboration with researchers in Germany: Marc Weidenbach, Drs. Maya Bar-Sadan and Lothar Houben of the Forschungszentrum Jülich, and Dr. Andrey N. Enyashin and Prof. Gotthard Seifert of the Technische Universität Dresden.
Prof. Reshef Tenne is Head of the Helen and Martin Kimmel Center for Nanoscale Science; and his research is supported by the Phyllis and Joseph Gurwin Fund for Scientific Advancement. Prof. Tenne is the incumbent of the Drake Family Professorial Chair in Nanotechnology.
(l-r) Yaara Yeshurun, Prof. Noam Sobel, Dr. Sagit Shushan, Liron Rozenkrantz, Idan Frumin and Shani Gelstein. The smell of tears
When we cry – a universal human behavior – we clearly send all sorts of emotional signals. Now, Institute scientists have shown that some of those emotional signals are chemically encoded in the tears themselves: In research that recently appeared in Science, they demonstrated that merely sniffing a woman’s tears – even when the crying woman is nowhere in the vicinity – reduces sexual arousal in men.
Humans, like most animals, expel various compounds in body fluids that give off subtle messages to other members of the species. A number of studies in recent years, for instance, have found that substances in human sweat can carry a surprising range of emotional and other signals to those who smell them.
But tears are odorless. In fact, in a first experiment led by Shani Gelstein, Yaara Yeshurun and their colleagues in the lab of Prof. Noam Sobel in the Weizmann Institute’s Neurobiology Department, the researchers tested whether men could discriminate the smell of saline from that of tears collected from female volunteers watching sad movies in a secluded room. The men could not.
Tears a turn-off
In a second experiment, male volunteers sniffed either tears or a control saline solution, and had these applied under their nostrils on a pad while they made various judgments regarding images of women’s faces on a computer screen. The next day, the test was repeated – the men who were previously exposed to tears got saline and vice versa. The tests were double-blinded, meaning neither the men nor the researchers performing the trials knew what was on the pads. The researchers found that sniffing tears did not influence how the men rated the sadness or empathy expressed in the women’s faces. To their surprise, however, it did have a negative effect on the sex appeal attributed to those faces.
To further explore the finding, male volunteers watched emotional movies after sniffing tears or saline. Throughout the movies, participants were asked to provide self-ratings of mood while they were being monitored for such physiological measures of arousal as skin temperature, heart rate, etc. Self-ratings showed that the subjects’ emotional responses to sad movies were no more negative when exposed to women’s tears; the men “smelling” tears showed no additional empathy. But they did rate their sexual arousal a bit lower. The physiological measurements, however, told a clearer story. These revealed a pronounced tear-induced drop in physiological measures of arousal, including a significant dip in testosterone – a hormone related to sexual arousal.
Finally, Sobel and his team repeated the previous experiment within an fMRI machine that allowed them to measure brain activity. The scans revealed a significant reduction in activity levels in the brain areas associated with sexual arousal after the subjects had sniffed tears.
Sobel: “This study raises many interesting questions. What is the chemical involved? Do different kinds of emotional situations send different tear-encoded signals? Are women’s tears different from, say, men’s tears? Children’s tears? This study reinforces the idea that human chemical signals – even ones we’re not explicitly conscious of – affect the behavior of others.”
Human emotional crying was especially puzzling to Charles Darwin, who identified functional antecedents to most emotional displays – for example, the tightening of the mouth in disgust, which he thought originated as a response to tasting spoiled food. But the original purpose of emotional tears eluded him. The current study has offered an answer to this riddle: Tears may serve as a chemosignal. Sobel points out that some rodent tears are known to contain such chemical signals. “The uniquely human behavior of emotional tearing may not be so uniquely human after all,” he says.
The work was authored by Shani Gelstein, Yaara Yeshurun, Liron Rozenkrantz, Sagit Shushan, Idan Frumin, Yehudah Roth and Noam Sobel, and was conducted in collaboration with the Edith Wolfson Medical Center, Holon.
Prof. Noam Sobel's research is supported by the James S. McDonnell Foundation 21st Century Science Scholar in Understanding Human Cognition Program; the Minerva Foundation; the European Research Council; and Regina Wachter, NY.
Drs. Rotem Sorek and Adi Stern. Bacteria's Achilles heel
Can a bacterium get rheumatoid arthritis? Not quite, but new research at the Weizmann Institute of Science shows that bacteria can suffer from a type of autoimmune disease – one in which their immune system mistakenly attacks their own cells, just as it does in human autoimmune diseases. In the case of the bacterium, such disease can kill it or leave its immune system crippled.
In autoimmune disease, the immune system that clears the body of harmful invaders seems to get confused, identifying the body’s own proteins as foreign and attacking them. Nonetheless, the immune system is a necessity, even in bacteria: Viruses that infect and kill bacteria are abundant; without an immune system, bacteria would have become extinct. In the past, scientists had assumed that bacteria had only the crudest of immune systems to aid them in fighting viral infection – one that is set in the genes and passed on unchanged to further generations. Only recently was it discovered that many bacteria have a second, more sophisticated kind of immune system, known as an adaptive immune system because it can learn to fight a virus it has never encountered before.
“In fact,” says Dr. Rotem Sorek of the Institute’s Molecular Genetics Department, “the bacterial immune system seems to have an advantage over the human version of adaptive immunity, because it not only stores information on previous bouts of infection, as in humans, but also passes the immunity on to daughter cells in its genes. As opposed to human infants, whose adaptive immune system is more or less a blank slate at birth, new bacteria benefit from the experience of the parents’ illnesses.”
The bacterial adaptive immune system is much simpler than of its counterpart in humans, but the principle is similar: Identify certain molecular patterns of the invader and then generate antibodies that attack anything with a matching pattern. The bacteria accomplish this using a genetic system known by the acronym CRISPR. During the first encounter with an invading virus, CRISPR captures snippets of viral DNA and holds them in so-called “immunity cassettes” in the bacterial genome. In subsequent infections, the CRISPR system uses these cassettes to produce small RNA molecules that act as antibodies, binding to the viral genetic material and blocking the viruses from replicating. These DNA samples are kept “on file,” and new immunity cassettes are added in anticipation of future threats.
To understand the bacterial immune system, Dr. Adi Stern, a postdoctoral fellow in Sorek’s group, together with Sorek, analyzed existing data on thousands of CRISPR immune cassettes. What they saw took them by surprise: Every once in a while a bit of the bacterium’s own DNA, rather than that of a virus, showed up as an immunity cassette. After further analysis, they realized that capturing self-DNA in the immune cassette that was supposed to hold viral DNA was a mistake that had drastic consequences for the bacterium: Its own DNA came under autoimmune attack. “To survive,” says Sorek, “the bacteria ended up shutting down their adaptive immune systems. Their only other option was to die. We really didn’t expect to find this kind of disease – one we think of as affecting only higher animals – in bacteria.”
Sorek: “Clearly, there’s a cost to having a sophisticated immune system. Only about half of all bacteria have adaptive immune systems; we think the risk of autoimmune disease might be too high for some. This twist gives us a new perspective on the tangled evolution of infection and immunity: Viruses evolve rapidly to evade the adaptive immune system, which races to keep up. In this fierce competition, it becomes harder and harder to distinguish between ‘self’ and ‘other,’ and mistakes may be the natural consequence.”
“Our goal now,” adds Sorek, "is to understand how we might induce this autoimmunity in bacteria. If we manage to inflict autoimmunity on disease-causing bacteria, we will make them more vulnerable and help our bodies to clear them more easily. Ironically, we plan to use the defense mechanism of bacteria as a weapon against them. This opens an exciting window on the development of new antibiotics.”
Dr. Rotem Sorek’s research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine; the Abisch Frenkel Foundation for the Promotion of Life Sciences; the Phyllis and Joseph Gurwin Fund for Scientific Advancement; and the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Sorek is the incumbent of the Rowland and Sylvia Schaefer Career Development Chair in Perpetuity.
Prof. Ernesto Joselevich and Tohar Yarden. Golden touch
King Midas may have turned everything he touched to gold, but he never got his hands on carbon nanotubes. That feat has been left to Prof. Ernesto Joselevich and research student Tohar Yarden of the Chemistry Faculty’s Materials and Interfaces Department. The two recently applied a technique, developed in Joselevich’s lab for directing the production of carbon nanotubes, to create, among other things, intricately shaped gold nanowires.
Two years ago, Joselevich and his research team began fabricating long, thin carbon nanotubes that bend, loop and curve into various shapes, including radiator-like serpentines that hinted at possible uses in nanodevices. Interestingly enough, these tiny shapes are self-organizing. By creating a sort of “ordered chaos,” in which fluctuations drive tube formation, the scientists found it was possible to “draw” any pattern they desired with these continuous carbon nanotubes.
Gold-plated serpentine carbon nanotubes
Now, the scientists have begun gold-plating these nanotube shapes through a process called electrodeposition. Electrical pulses cause dissolved metal salts to leave the solution and attach to the nanotubes. Lovely as these creations appear, the idea is not to design microscopic jewelry, says Joselevich, but “to combine the unique geometry of the serpentine nanotubes with the properties of other materials.” Any material that is a conductor or semiconductor can be used to make nanowires with this method, which, in their recent publication in Nano Letters, the researchers called "drawing with nanotubes.” In addition to gold, they coated serpentine nanotubes with bismuth telluride, a material that has the ability to convert heat to electricity or, conversely, cool when electricity passes through. Nanowires of bismuth telluride could power microscopic devices or function as miniature cooling units for nanoelectronics.
The team is continuing to experiment with creating serpentine nanowires from a variety of materials. A recent effort might be used, for instance, in miniature light collectors or sensors, or even “nano-neon” lights.
Prof. Ernesto Joselevich's research is supported by the Carolito Stiftung.
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Better Bonds with Water