“Moving mountains” is synonymous with doing the impossible. Yet at least once in the past, one mountain actually picked up and moved a fair distance away. This feat took place around 50 million years ago, in the area of the present-day border between Montana and Wyoming. Heart Mountain was part of a larger mountain range when the 100-km- (62-mile-) long ridge somehow became detached from its position and shifted about 50 km to the southwest. Scientists first realized that the peak was not in its original spot when they discovered that the rock formation underneath was younger than the mountain sitting on top of it. Later satellite images helped them to place the original position of the mountain. This “migrating mountain” has garnered interest from geologists and geophysicists around the world, who have tried to solve the mystery behind the largest known instance of land movement on the face of any continent. Dr. Einat Aharonov of the Weizmann Institute’s Environmental Sciences and Energy Research Department, working in collaboration with Dr. Mark Anders of Columbia University in New York, published a paper in the scientific journal Geology that offers an explanation for the phenomenon.

 

In the scenario put forward by Aharonov and Anders, the mountain range was permeated with vertical cracks in the rock, called dikes, filled with hot lava boiling up from deep in the earth. This particular range had a relatively large number of these dikes, creating conduits in the rock leading from the lava source many thousands of meters below the surface upward to a 3-kilometer-deep aquifer – a porous, water-soaked layer of limestone. There, the sizzling lava would have heated the water to extreme temperatures, causing the pressure in the trapped fluid to rise tremendously. The scientists developed a mathematical model (based on the number of dikes in the mountain and their structure) that enabled them to calculate the temperatures and pressures that would have been created deep within the base of the mountain. The results showed that the hot lava would have turned the water in the aquifer layer into a sort of giant pressure cooker, releasing enough force to literally move a mountain.   

 

 

 

 

From dashing off an e-mail to writing War and Peace, communicating thoughts and meanings involves translating a complex idea or set of ideas into a one-dimensional string of words that another person can read in sequence and then recreate the meaning in his or her mind. Communication is at once one of the most basic and  the most mysterious of our daily activities: Everyone does it; few are really good at it.

Is there a basic, underlying structure to the effective communication of complex ideas? A team of scientists that included physicists and language researchers at the Weizmann Institute of Science and elsewhere investigated this question by applying scientific methods to some of our culture’s most successful models for the skillful transfer of ideas: classic writings that, by common agreement, get their messages across well. In research published in the Proceedings of the National Academy of Sciences (PNAS), the scientists created mathematical tools that allowed them to trace the development of ideas throughout a book. The international team included Prof. Elisha Moses and postdoctoral fellow Dr. Enrique Alvarez Lacalle of the Weizmann Institute’s Physics of Complex Systems Department as well as Prof. Jean-Pierre Eckmann, a frequent visitor from the University of Geneva, and research student Beate Dorow from the University of Stuttgart.

Because strings of words are one-dimensional, they literally lack depth. Yet our minds and memories are able to recreate complex ideas from this string. Moses and his team hypothesized that this process may rely on hierarchical structures “encoded” in the narrative. (An obvious hierarchical structure in a text is chapter-paragraph-sentence.) The implication is that our minds decipher not only the individual words, but the encoded structure, enabling us to comprehend abstract concepts.

The scientists applied their mathematical tools to a number of books known for their ability to convey ideas. They included the writings of Albert Einstein, Mark Twain’s Tom Sawyer, Metamorphosis by Franz Kafka and other classics of different styles and periods, to see if it was possible to identify common structures. They defined “windows of attention” of around 200 words (about a paragraph), and within these windows, they identified pairs of words that frequently occurred near each other (after eliminating “meaningless” words such as pronouns). From the resulting word lists and the frequency with which the single words appeared in the text, the scientists’ mathematical analysis was used to construct a sort of network of “concept vectors” – linked words that convey the principal ideas of the text.

Mathematically, these concept vectors can go in many directions. When we read a text, we’re taking a tour along the paths that make up the resulting network. The multidimensional concept vectors seem to span a whole “web” of ideas. The scientists’ findings suggest that this network is based on a tree-like hierarchy, and that such a hierarchy may be a basic underpinning of all language. The reader or listener can reconstruct the hierarchical structure of a text and so enter the multidimensional space of ideas. Thus, from a flat page and a one-dimensional string of words, we are able to grasp the full complexity of “the author’s meaning.”

Moses: “Philosophers from Wittgenstein to Chomsky have taught us that language plays a central evolutionary role in shaping the human brain, and that revealing the structure of language is an essential step to comprehending brain structure. Our contribution to research in this basic field is in using mathematical tools to connect concepts or ideas with the words used to express them. The structure serves to transmit concepts and reconstruct them in the mind of the reader. A deep question that remains open is whether the correlations we uncovered are related to making a text aesthetic as well as comprehensible.” 

 
 

 

 

The volunteer sits with earphones on his head and an electrode taped to his finger, tapping to a beat. Suddenly, his forefinger swings out of rhythm. The researcher standing behind him, postdoctoral fellow Dr. Nestor Handzy, has aimed a painless, external magnetic pulse at one part of his brain, which causes the finger to twitch involuntarily. For that split second, explains Handzy, the finger’s actions were controlled by two opposing instructions. This sort of competition, says Prof. Moses, lends itself to treatment with concepts from physics.

Moses and Handzy have teamed up with Dr. Avi Peled of the Technion and Shaar Menashe Mental Health Center, a psychiatrist who believes that physics can help find better treatments for schizophrenia. In Peled’s words: “The brain is an extremely complex, non-linear network of neurons, and schizophrenia is probably a disorder of connectivity.” Moses: “As physicists, we framed the question and set up the experiment using a complex systems approach.”

With the simple finger-tapping test, the team has already found that schizophrenics’ brains show an atypical response pattern. What’s more, they’ve seen evidence that magnetic pulses might be able to straighten out skewed lines of communication between brain areas in schizophrenia patients. The scientists’ dream is to eventually create a “brain pacemaker” to “reset” these faulty communication signals.

 

 

 

 

 

 

 

 

 

 

 

 

 

In an emotionally difficult situation, it’s easy to feel as though we are “eating ourselves up from the inside.” In humans, this is no more than a psychological feeling, but for cells in our body, getting eaten from the inside can really happen. Every one of our cells is uploaded with a special “program” that instructs the cell to abort if it becomes a threat to the body – if it begins to turn cancerous, for example. This phenomenon of cellular suicide can occur in two different ways. The most commonly known is named “apoptosis” (in Greek: “falling off,” like leaves from a deciduous tree). In apoptosis, the cell produces toxic proteins that cause it to break apart. Cells that kill themselves in this way are “eaten” by neighboring cells. The second cellular suicide method, called autophagy, occurs when the cell literally eats itself from within. Malfunctions in these self-destruct programs may result in diseases such as cancer.

 

Prof. Adi Kimchi, Head of the Molecular Genetics Department, and research student Sharon Reef recently identified a novel protein that tells the cancerous cell to choose the self-eating method of suicide. In research that was published in the journal Molecular Cell, Kimchi and Reef discovered that this new protein is actually a shortened version of a previously known protein that usually causes apoptosis. These two proteins are in fact encoded by the same gene, even though each instructs the cancerous cell to commit suicide in a different way. The scientists proved that the shorter version of the protein, due to the missing segment, carries out its activity in an area of the cell completely different from that used by the longer protein. Consequently, autophagy is
triggered instead of apoptosis. 

 

The process of autophagy is based on the concept of “recycling bins”: double-membraned sac-like structures that actively develop in the cells. Especially during times of starvation, when food is lacking, these bins are able to recycle some of the cell’s contents, providing it with extra food and energy. But under certain circumstances, the recycling bins work in overdrive mode, resulting in self-eating to the point of death. The question arose: Is the observed autophagy – that triggered by the novel protein – a survival mechanism or its opposite, an agent of self-destruction? 

 

To answer the question, Kimchi and Reef, together with Einat Zalckvar and Shani Bialik of the Molecular Genetics Department and Prof. Moshe Oren and Ohad Shifman of the Molecular Cell Biology Department, silenced two genes that are known to be necessary for assembling the sac-like autophagic “recycling bins.” They discovered that reducing the occurrence of autophagy via gene silencing increased the survival of cells and thus concluded that the formation of the membrane-bound sacs in this case spells total degradation for the cells’ contents. 

 

But why have two different suicide mechanisms developed in cells? Kimchi suggests that the autophagy track is a sort of back-up plan, in case the cancer cell fails – for a variety of possible reasons – to sacrifice itself by apoptosis. By employing a back-up plan, the cell continues to ensure the prevention of the spread of cancer. Now the scientists plan to check if their understanding is correct, or whether autophagy is an independent process, unrelated to the cell's  earlier failed attempts to commit apoptosis.    

  
Prof. Adi Kimchi’s research is supported by the Clore Center for Biological Physics; the Leo and Julia Forchheimer Center for Molecular  Genetics; the Levine Institute of Applied Science; the Jeans-Jacques Brunschwig Fund for the Molecular Genetics of Cancer; the Joseph and Bessie Feinberg Foundation; the Flight Attendant Medical Research Institute; the Anne P. Lederer Research Institute; the Lombroso Prize for Cancer Research; the Ruth and Samuel Rosenwasser Charitable Fund; and the Jacqueline Seroussi Foundation Israel. Prof. Kimchi is the incumbent of the Helena Rubinstein Professorial Chair in Cancer Research.

 

 

 

 

 

 

 

 

 

 

 

Anyone who’s had the experience of putting machinery back together and having a part left over knows that some parts are more essential than others. Prof. Zvulun Elazar of the Biological Chemistry Department has used this principle to identify, for the first time, two sites on a particular yeast protein that are indispensable for protein recognition. Without these recognition sites, the process of assembling the “recycling bins” needed for cellular self-eating can’t take place. 

 

For the protein to carry out its activity, a specific, complementary protein needs to recognize and “plug” into one of its “sockets” – an action that initiates a cascade of events. By removing various socket-like structures one at a time from the protein and seeing how this affected the overall working of the autophagic machine, Elazar and his research team were able to isolate the specific site the second protein must recognize and hook up to. When this site was missing, that protein remained unplugged, leaving the cellular recycling machinery idle. They also found a second site on the protein that appears to be necessary for autophagic activity, although how it works needs to be studied further. 

 

Autophagy in mammalian cells has significant associations with neurodegenerative diseases, heart disease, cancer, program-med cell death, and bacterial and viral infections. Because the autophagic recycling system found in yeast is similar to that in mammals, this research could provide crucial insight for further studies into the malfunctioning of cellular machinery and its consequences.

 

This research, which was published in EMBO Reports, was conducted with Ph.D. students Nira Amar of the Biological Chemistry Department and Gila Lustig of the Biological Regulation Department, in collaboration with Dr. Yoshinobu Ichimura and Prof.Yoshinori Ohsumi of the National Institute for Basic Biology, Japan.
  
Prof. Zvulun Elazar’s research is supported by the Philip M. Klutznick Fund for Research; Mr. and Mrs. Stanley Chais, Beverly Hills, CA; and Mr. and Mrs. Mitchell Caplan, Bethesda, MD.

 

 

How do our brains stay healthy? Until quite recently, most scientists believed each brain is allotted a fixed number of nerve cells that gradually degenerate and die without being replaced. Fortunately for us, science has since overturned this dogma: Certain regions of the adult brain do, in fact, retain their ability to maintain cell renewal throughout life. But this discovery raises new riddles: How does the brain know when and how to produce new brain cells?

 

This question has been puzzling scientists, mainly because the central nervous system (CNS) - the brain and spinal cord - has been viewed as a sort of Forbidden City, guarded by well-established border controls. These controls supposedly prevent the entry of immune system cells - the cells responsible for fighting infection and promoting healing and renewal - as they present a possible threat to the complex and dynamic nerve cell networks. Immune cells that recognize the body’s own components (autoimmune cells) are considered even more dangerous, as they can induce autoimmune diseases. Although autoimmune cells are often detected in a healthy CNS, their presence there is generally explained as a failure of the body’s "border police" to eliminate them.

 

A team led by Prof. Michal Schwartz of the Weizmann Institute’s Neurobiology Department, however, has a different explanation. They had demonstrated that strictly controlled levels of autoimmune cells have the potential to fight off debilitating degenerative conditions that can afflict the CNS, such as Alzheimer’s and Parkinson’s diseases, glaucoma and nerve degeneration resulting from trauma or stroke. Earlier research by Schwartz and her team suggested that these T cells - specialized immune cells that have the ability to recognize CNS components - are not enemies attacking the brain but friendly forces that help the brain to safely fight off outflows of toxic substances from damaged nerve tissues.

 

In a recent study published in Nature Neuroscience, the scientists showed that, in addition to preventing disease, these immune cells may be key players in the body’s campaign to maintain a normal, healthy brain. They worked with rats kept in an environment rich in mental stimulation and opportunities for physical activity, which is known to fuel the formation of new nerve cells in the hippocampus (a memory-related brain region). The Weizmann Institute scientists showed for the first time that this nerve cell renewal (called neurogenesis) is linked to local immune activity. But are T cells really to thank for this, as Schwartz suspected, or are other factors responsible?

 

To answer this question, the team conducted a series of experiments. They first repeated the above experiment using mice that lack a number of important immune cells, including T cells. Though housed in an enriched environment, these immunodeficient mice didn’t exhibit the increase in brain-cell renewal seen in the trials with normal mice. When the scientists repeated the experiment, this time with mice missing only the T cells, they again found impaired neurogenesis, confirming that T cells themselves were the critical factor in forming new brain cells.

 

Schwartz points out that autoimmune T cells don’t affect levels of intelligence or motivation; rather, they allow the organism to achieve the full potential of its brainpower. "These findings," she says, "give new meaning to ‘a healthy mind in a healthy body.’ They open up exciting new prospects for the treatment of cognitive loss." Knowledge that the immune system contributes to nerve cell renewal may have far-reaching implications for the elderly, in particular, because aging is known to be associated with a drop in immune system function accompanied by a decrease in new brain cell formation and memory skills. By manipulating and boosting the immune system, it might be possible to prevent or slow age-related memory loss.

 

 

In addition to the maintenance of brain cell renewal and cognitive abilities, T cells that recognize brain antigens may improve the ability of mice to cope and to adapt their behavior to stressful life events. Mice that lack these cells manifest responses typical of those of post-traumatic stress disorder (PTSD). This finding of Drs. Cohen and Kipnis and Prof. Schwartz's team has recently been published in the Journal of Neurobiology.

 

Schwartz says that these results may, in the future, lead to the development of T-cell-based vaccines, which might be used to help prevent the development of PTSD following stressful episodes.