Diminishing at the Edges

TAU study reveals: overfishing severely harms marine protected areas around the world

A new study by Tel Aviv University reveals significant ecological damage to many marine protected areas (MPAs) around the world. A strong “edge effect” was observed, resulting in a 60% reduction in the fish population living on their outer edges (1-1.5 km), compared to the core areas. The “edge effect” significantly diminishes the effective size of those areas, and largely stems from human pressures, first and foremost overfishing at their borders.

Marine protected areas were designed to preserve marine ecosystems, and help to conserve and restore fish populations and marine invertebrates whose numbers are increasingly dwindling due to overfishing. The effectiveness of the protected areas has been proven in thousands of studies conducted worldwide. At the same time, most studies sample only their “inside” and “outside”, and there still is a knowledge gap about what happens in the space between their core and areas around them that are open for fishing.

The study was conducted by Sarah Ohayon, a doctoral student at the laboratory of Prof. Yoni Belmaker, School of Zoology, The George S. Wise Faculty of Life Sciences, and The Steinhardt Museum of Natural History at Tel Aviv University. The study was recently published in the Nature Ecology & Evolution Journal.

 

The “Edge Effect”

When a protected area functions properly, the expectation is that the recovery of the marine populations within it will result in a spillover, a process where fish and marine invertebrates migrate outside its borders. In this way, the protected area can contribute not only to the conservation of marine nature, but also to the renewal of fish populations surrounding it that have dwindled due to overfishing.

To identify the dominant spatial pattern of marine populations from within the protected areas to the surrounding areas (that are open for fishing), the researchers analyzed marine populations from dozens of protected areas located in different parts of the oceans. 

“When I saw the results, I immediately understood that we are looking at a pattern of edge effect”, says Ohayon. “The edge effect is a well-studied phenomenon in terrestrial protected areas, but surprisingly it has not yet been studied empirically in MPAs. “This phenomenon occurs when there are human disturbances and pressures around the protected area, such as hunting/fishing, noise or light pollution that reduce the size of natural populations within the protected areas, close to their borders”.

 

No-Take Marine Protected Areas Are Too Small

The researchers found that 40% of the no-take MPAs (areas where fishing activity is completed prohibited) around the world are less than 1 km2, which means that entire area is likely to experience an edge effect. In total, 64% of all no-take MPAs in the world are smaller than 10 km2 and may hold only about half (45-56%) of the expected population size in their area compared to a situation without an edge effect. These findings indicate that the global effectiveness of existing no-take areas is far less than previously thought.

It should be emphasized that the edge effect pattern does not eliminate the possibility of fish spillover, and it is quite plausible that fishers still enjoy large fish coming from within the protected areas. This is evidenced by the concentration of fishing activity at their borders. At the same time, the edge effect makes it clear to us that marine populations near the borders of the protected areas are declining at a faster rate than the recovery of the populations surrounding them.

 

Buffer, Enlarge and Enforce

The study findings also show that in protected areas with buffer zones around them, no edge effect patterns were recorded, but rather a pattern consistent with fish spillover outside their borders. Additionally, a smaller edge effect was observed in well-enforced protected areas than in those where illegal fishing was reported.

“These findings are encouraging, as they signify that by putting buffer zones in place, managing fishing activity around marine protected areas and improving enforcement, we can increase the effectiveness of the existing protected areas and most probably also increase the benefits they can provide through fish spillover”, adds Ohayon.

“When planning new marine protected areas, apart from the implementation of regulated buffer zones, we recommend that the no-take MPAs targeted for protection be at least 10 km2 and that their shape be as round as possible. These measures will reduce the edge effect. Our research findings provide practical guidelines for improving the planning and management of marine protected areas, so that we can do a better job of protecting our oceans.” 

Featured image: Photo credit Dr. Shevy Rothman

For the first time: The “God Particle” has been characterized in its decay into a pair of charm quarks

TAU researchers contribute further understanding of elusive elementary particle that gives mass to everything in the universe

Physicists worldwide have been captivated by the Higgs boson particle, also known as the “God Particle”. Its discovery a decade ago made waves in the physics community, and had researchers curious to learn more about its properties. TAU researchers have now succeeded, as part of a groundbreaking study, to describe a rare physical process through which the Higgs boson decays into a pair of rare elementary particles. The rate of this decay process can now be characterized more precisely and completely than before.

The new study was conducted as part of the ATLAS experiment at the Large Hadron Collider (LHC) at CERN (Geneva) by Prof. Erez Etzion and doctoral students Guy Koren, Hadar Cohen and David Reikher from the Raymond and Beverly Sackler School of Physics and Astronomy, Raymond and Beverly Sackler Faculty of Exact Sciences, at Tel Aviv University. It was a collaboration with the research team of Prof. Eilam Gross from the Weizmann Institute of Science and others.

Learning More About Forces in Nature

Over fifty years ago, physicists Prof. Peter Higgs and Prof. Francois Englert (who since 1984 has been a Sackler Fellow by special appointment in the TAU School of Physics and Astronomy) estimated that a new particle might exist whose field “provides the mass” to the elementary particles in our world.

In 2012, the end of a 30-year hunt for the Higgs boson was celebrated. Israeli researchers were senior partners in this discovery, and Prof. Halina Abramowicz, who was part of the TAU team, said “The discovery of the Higgs-like particle affirms the world view that the universe is made up of straightforward, symmetrical laws and that humans are the byproduct of disruptions in that symmetry.” Higgs and Englert won the Nobel Prize the following year.

The Challenge of Creating the Higgs boson 

In the particle accelerator, pairs of protons are made to collide with each other at extremely high velocities. In such energetic collisions, various interesting processes can occur, from which, one can learn about the nature of our universe. The way in which these processes are investigated, is by means of a complex array of particle detectors placed around the points of collision, enabling reconstruction of the types of particles that are generated during the collision, as well as their features. A vast range of processes can occur during the collisions, and each has its own unique “signature” in the detector. In order to extract rare events and acquire new insights about the elementary particles and forces in nature, large amounts of statistical data must be collected (i.e. a very large number of collisions must be observed).

The Higgs boson is, as mentioned, a relatively heavy elementary particle, but can be created in collision between protons, as long as the accelerator’s energy is high enough. Immediately after its creation, it decays into lighter particles.

“It is interesting to investigate into which types of particles the Higgs decays, and with what frequency it decays into each type of particle,” says Guy Koren. “To help answer that question, our group is trying to measure the rate at which the Higgs boson decays into particles called ‘charm quarks’.” Quarks are a specific type of particles that share similar features. They compound, for instance, the protons and neutrons, which are in the nuclei of atoms. Koren continues to explain that measuring the decay of Higgs boson into ‘charm quarks’ is not a simple mission, for two reasons: 1. Only one out of billions of collisions [between protons] result in the creation of Higgs bosons. Furthermore, only three percent of the Higgs bosons that do emerge proceed to decay into charm quarks. 2. Five additional types of quarks exist, and they all leave similar signatures in the detectors. So, even when the process does take place, it is very hard to identify.

More Information About The Rate of Decay 

Despite all the collisions that have been collected since 2012, the group from Tel Aviv has not yet identified enough decays of Higgs bosons into charm quarks to measure the rate of the process with the required statistical accuracy.

Nevertheless, sufficient data has been accumulated to state what the maximal rate of the process is with respect to the theoretical predictions. A rate of decay higher than the predicted rate would constitute a first important indicator for “new” physics or expansion of the currently accepted model – the standard model of elementary particles. From the current measurement, the researchers conclude (with a well-defined statistical certainty) that there is no chance that the rate of decay of the Higgs boson into charm quark is 8.5 (or more) times higher than the theoretical predictions, otherwise enough such decays would have been observed in order to measure it. “This is the first time that anyone has ever succeeded in saying something important about the rate of this specific decay based on a direct measurement of it, therefore it is a very important and significant statement in our field,” explains Koren

The research is not yet over, however. Higgs’ decays into quarks of smaller masses have yet to be observed. As a result, the researchers cannot be certain that the same ‘rules’ apply to quarks from those generations. “If it should appear that the Higgs boson decays at a rate that is not proportional to mass (squared) of the particles, there could be far-reaching implications for our understanding of the universe,” explains Prof. Etzion.

Featured image: Illustration: The European Organization for Nuclear Research (CERN)’s LHC accelerator, by which the Higgs boson was detected in 2012 in the ATLAS and CMS experiments

A world first: Technology that restores the sense of touch in nerves damaged as a result of amputation or injury

Cut your finger and lost your sense of touch? There’s hope yet.

  • Researchers have developed a sensor that can be implanted anywhere in the body, for example under the tip of a severed finger; the sensor connects to another nerve that functions properly and restores tactile sensation to the injured nerve.
  • This unique development is biocompatible (“human-body friendly”) and does not require electricity, wires, or batteries.

Tel Aviv University’s new and groundbreaking technology inspires hope among people who have lost their sense of touch in the nerves of a limb following amputation or injury. The technology involves a tiny sensor that is implanted in the nerve of the injured limb, for example in the finger, and is connected directly to a healthy nerve. Each time the limb touches an object, the sensor is activated and conducts an electric current to the functioning nerve, which recreates the feeling of touch. The researchers emphasize that this is a tested and safe technology that is suited to the human body and could be implanted anywhere inside of it once clinical trials will be done.

The technology was developed under the leadership of a team of experts from Tel Aviv University: Dr. Ben M. Maoz, Iftach Shlomy, Shay Divald, and Dr. Yael Leichtmann-Bardoogo from the Department of Biomedical Engineering, Fleischman Faculty of Engineering, in collaboration with Keshet Tadmor from the Sagol School of Neuroscience and Dr. Amir Arami from the Sackler School of Medicine and the Microsurgery Unit in the Department of Hand Surgery at Sheba Medical Center. The study was published in the prestigious journal ACS Nano.

The researchers say that this unique project began with a meeting between the two Tel Aviv University colleagues – biomedical engineer Dr. Maoz and surgeon Dr. Arami. “We were talking about the challenges we face in our work,” says Dr. Maoz, “and Dr. Arami shared with me the difficulty he experiences in treating people who have lost tactile sensation in one organ or another as a result of injury. It should be understood that this loss of sensation can result from a very wide range of injuries, from minor wounds – like someone chopping a salad and accidentally cutting himself with the knife – to very serious injuries. Even if the wound can be healed and the injured nerve can be sutured, in many cases the sense of touch remains damaged. We decided to tackle this challenge together, and find a solution that will restore tactile sensation to those who have lost it.”

In recent years, the field of neural prostheses has made promising developments to improve the lives of those who have lost sensation in their limbs by implanting sensors in place of the damaged nerves. But the existing technology has a number of significant drawbacks, such as complex manufacturing and use, as well as the need for an external power source, such as a battery. Now, the researchers at Tel Aviv University have used state-of-the-art technology called a triboelectric nanogenerator (TENG) to engineer and test on animal models a tiny sensor that restores tactile sensation via an electric current that comes directly from a healthy nerve and doesn’t require a complex implantation process or charging.

The researchers developed a sensor that can be implanted on a damaged nerve under the tip of the finger; the sensor connects to another nerve that functions properly and restores some of the tactile sensation to the finger. This unique development does not require an external power source such as electricity or batteries. The researchers explain that the sensor actually works on frictional force: whenever the device senses friction, it charges itself.

The device consists of two tiny plates less than half a centimeter by half a centimeter in size. When these plates come into contact with each other, they release an electric charge that is transmitted to the undamaged nerve. When the injured finger touches something, the touch releases tension corresponding to the pressure applied to the device – weak tension for a weak touch and strong tension for a strong touch – just like in a normal sense of touch.

The researchers explain that the device can be implanted anywhere in the body where tactile sensation needs to be restored, and that it actually bypasses the damaged sensory organs. Moreover, the device is made from biocompatible material that is safe for use in the human body, it does not require maintenance, the implantation is simple, and the device itself is not externally visible.

According to Dr. Maoz, after testing the new sensor in the lab (with more than half a million finger taps using the device), the researchers implanted it in the feet of the animal models. The animals walked normally, without having experienced any damage to their motor nerves, and the tests showed that the sensor allowed them to respond to sensory stimuli. “We tested our device on animal models, and the results were very encouraging,” concludes Dr. Maoz. “Next, we want to test the implant on larger models, and at a later stage implant our sensors in the fingers of people who have lost the ability to sense touch. Restoring this ability can significantly improve people’s functioning and quality of life, and more importantly, protect them from danger. People lacking tactile sensation cannot feel if their finger is being crushed, burned or frozen.”

Dr. Maoz’s laboratory:

https://www.maozlab.com/

  The article:

https://pubs.acs.org/doi/full/10.1021/acsnano.0c10141

 

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New study found differences between women and men in the level of COVID-19 antibodies

Prof. Noam Shomron, Head of the Computational Genomics Laboratory at the Sackler Faculty of Medicine and a member of the Edmond J. Safra Center for Bioinformatics

A joint study conducted by researchers from Tel Aviv University and the Shamir Medical Center (Asaf Harofe) examined the level of antibodies in over 26,000 blood samples taken from COVID-19 convalescents, as well as vaccinated and unvaccinated individuals. The serological results indicate that the level of antibodies changes according to age groups, gender, symptoms, and time elapsed since vaccination. The study was published in Medrxiv.

A difference was found between vaccinated women and men, in the concentration of antibodies in the blood relative to both age and gender. In women, the level of antibodies begins to rise from the age of 51, and is higher than the levels found in men of similar age. This phenomenon may be related change in levels of the estrogen hormone, observed around this age, which affects the immune system. In men, a rise in antibody levels is seen at an earlier age, starting around 35. This may be related to changes in levels of the male sex hormone testosterone, and the effect on the immune system.

In young adults, a high concentration of antibodies is usually the result of a strong immune response, while in older people it typically indicates overreaction of the immune system associated with severe illness.

Dr. Adina Bar Chaim from the Shamir Medical Center

Main trends and findings:

  1. The immune response of individuals who have received two doses of the vaccine is much stronger than that of people who have recovered from COVID-19. In fact, the level of antibodies found in the blood of vaccinated persons was 4 times higher than that found in convalescents.
  2. A difference was found between convalescent males and females – in antibody concentration in the blood relative to both age and gender. In women, the concentration begins to rise from the age of 51, and it is higher than the levels found in men of similar age. This phenomenon may be related to the change in levels of the estrogen hormone, observed around this age, which affects the immune system. In men, a rise in antibody levels is seen at an earlier age, starting around 35. This may be related to changes in levels of the male sex hormone testosterone, and its effect on the immune system.

In young adults, a high concentration of antibodies is usually the result of a strong immune response, while in older people it usually indicates overreaction of the immune system associated with severe illness.

  1. In general, young adults were found to have a higher level of antibodies sustained for a longer period of time compared to older vaccinated persons. A decrease of tens of percent was observed over time between the younger and very old age groups.

Conclusion: Further research is required in order to obtain an in-depth understanding of the immune system’s response to COVID-19, to recovery from the disease, and to the vaccine. We hope that in the future we will be able to supply a reliable measure for the effectiveness of vaccination, correlated with age, gender and symptoms.

The study was conducted by Tel Aviv University’s Prof. Noam Shomron, Head of the Computational Genomics Laboratory at the Sackler Faculty of Medicine and a member of the Edmond J. Safra Center for Bioinformatics and Dr. Adina Bar Chaim from the Shamir Medical Center. The data were collected by Dr. Ramzia Abu Hamad from the Shamir Medical Center, and analysis was conducted by Guy Shapira, a PhD student at Prof. Shomron’s laboratory.

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When the stars aligned: A star in a distant galaxy blew up in a powerful explosion, solving an astronomical mystery from the 11th century

Las Cumbres Observatory and Hubble Space Telescope color composite of the electron-capture supernova 2018zd (the large white dot on the right) and the host starburst galaxy NGC 2146 (toward the left).

Giant Explosion in Space Illuminates Thousand-Year Mystery.

Dr. Iair Arcavi.
Credit: Israel Hadari 

Dr. Iair Arcavi, a Tel Aviv University researcher at the Raymond and Beverly Sackler Faculty of Exact Sciences, participated in a study that discovered a new type of stellar explosion – an electron-capture supernova. While they have been theorized for 40 years, real-world examples have been elusive. Such supernovas arise from the explosions of stars 8-9 times the mass of the sun. The discovery also sheds new light on the thousand-year mystery of the supernova from A.D. 1054 that was seen by ancient astronomers, before eventually becoming the Crab Nebula, that we know today.

A supernova is the explosion of a star following a sudden imbalance between two opposing forces that shaped the star throughout its life. Gravity tries to contract every star. Our sun, for example, counter balances this force through nuclear fusion in its core, which produces pressure that opposes the gravitational pull. As long as there is enough nuclear fusion, gravity will not be able to collapse the star. However, eventually, nuclear fusion will stop, just like gas runs out in a car, and the star will collapse. For stars like the sun, the collapsed core is called a white dwarf. This material in white dwarfs is so dense that quantum forces between electrons prevent further collapse.

For stars 10 times more massive than our sun, however, electron quantum forces are not enough to stop the gravitational pull, and the core continues to collapse until it becomes a neutron star or a black hole, accompanied by a giant explosion. In the intermediate mass range, the electrons are squeezed (or more accurately, captured) onto atomic nuclei. This removes the electron quantum forces, and causes the star to collapse and then explode.

Historically, there have been two main supernova types. One is a thermonuclear supernova — the explosion of a white dwarf star after it gains matter in a binary star system. These white dwarfs are the dense cores of ash that remain after a low-mass star (one up to about 8 times the mass of the sun) reaches the end of its life. Another main supernova type is a core-collapse supernova where a massive star — one more than about 10 times the mass of the sun — runs out of nuclear fuel and has its core collapsed, creating a black hole or a neutron star. Theoretical work suggested that electron-capture supernovae would occur on the borderline between these two types of supernovae.

That’s the theory that was developed in the 1980’s by Ken’ichi Nomoto of the University of Tokyo, and others. Over the decades, theorists have formulated predictions of what to look for in an electron-capture supernova. The stars should lose a lot of mass of particular composition before exploding, and the supernova itself should be relatively weak, have little radioactive fallout, and produce neutron-rich elements.  

The new study, published in Nature Astronomy, focuses on the supernova SN2018zd, discovered in 2018 by Japanese amateur astronomer Koihchi Itagaki. Dr. Iair Arcavi, of the astrophysics department at Tel Aviv University, also took part in the study. This supernova, located in the galaxy NGC 2146, has all of the properties expected from an electron-capture supernova, which were not seen in any other supernova. In addition, because the supernova is relatively nearby – only 31 million light years away – the researchers were able to identify the star in pre-explosion archival images taken by the Hubble Space Telescope. Indeed, the star itself also fits the predictions of the type of star that should explode as an electron-capture supernovae, and is unlike stars that were seen to explode as the other types of supernovae.

From left: Japanese amateur astronomer Koichi Itagaki (who discovered the supernova), Tel Aviv University researcher Dr. Iair Arcavi (who participated in the study), and University of California graduate student Daichi Hiramatsu (lead author of the study), at one of Itagaki’s telescopes in Japan.

While some supernovae discovered in the past had a few of the indicators predicted for electron-capture supernovae, only SN2018zd had all six – a progenitor star that fits within the expected mass range, strong pre-supernova mass loss, an unusual chemical composition, a weak explosion, little radioactivity, and neutron-rich material. “We started by asking ‘what’s this weirdo?’” said Daichi Hiramatsu of the University of California Santa Barbara and Las Cumbres Observatory, who led the study. “Then we examined every aspect of SN 2018zd and realized that all of them can be explained in the electron-capture scenario.”

The new discoveries also illuminate some mysteries of one of the most famous supernovae of the past. In A.D. 1054 a supernova happened in our own Milky Way Galaxy, and according to Chinese and Japanese records, it was so bright that it could be seen in the daytime and cast shadows at night. The resulting remnant, the Crab Nebula, has been studied in great detail, and was found to have an unusual composition. It was previously the best candidate for an electron-capture supernova, but this was uncertain partly because the explosion happened nearly a thousand years ago. The new result increases the confidence that the historic 1054 supernova was an electron-capture supernova.

“It’s amazing that we can shed light on historical events in the Universe with modern instruments,” says Dr. Arcavi. “Today, with robotic telescopes that scan the sky in unprecedented efficiency, we can discover more and more rare events which are critical for understanding the laws of nature, without having to wait 1000 years between one event and the next.”

Dr. Arcavi is a member of the Global Supernova Project, and makes use of the Las Cumbres telescope network to study rare transient phenomena like supernovae, neutron star mergers, and stars torn apart by black holes.

Link to the original article: https://www.nature.com/articles/s41550-021-01384-2

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First 3D-bioprinting of entire active tumor

Research team(Left to right): Eilam Yeini, Prof. Satchi-Fainaro and Lena Neufeld

Scientific breakthrough in the battle against cancer

The 3D print of glioblastoma – the deadliest type of brain cancer – is printed from human glioblastoma tissues containing all components of the malignant tumor

Researchers: the breakthrough will enable much faster prediction of best treatments for patients, accelerate the development of new drugs and discovery of new druggable targets

A scientific achievement for researchers at Tel Aviv University: printing an entire active and viable glioblastoma tumor using a 3D printer. The 3D-bioprinted tumor includes a complex system of blood vessel-like tubes through which blood cells and drugs can flow, simulating a real tumor.

Illustration.
Credit: Veronica Hughes, PhD of STEAM visuals

The study was led by Prof. Ronit Satchi-Fainaro, Sackler Faculty of Medicine and Sagol School of Neuroscience, Director of the Cancer Biology Research Center, Head of the Cancer Research and Nanomedicine Laboratory and Director of the Morris Kahn 3D-BioPrinting for Cancer Research Initiative, at Tel Aviv University.

The new technology was developed by PhD student Lena Neufeld, together with other researchers at Prof. Satchi-Fainaro’s laboratory:  Eilam Yeini, Noa Reisman, Yael Shtilerman, Dr. Dikla Ben-Shushan, Sabina Pozzi, Dr. Galia Tiram, Dr. Anat Eldar-Boock and Dr. Shiran Farber.  

The 3D-bioprinted models are based on samples from patients, taken directly from operating rooms at the Tel Aviv Sourasky Medical Center. The new study’s results were published today in the prestigious journal Science Advances.

“Glioblastoma is the most lethal cancer of the central nervous system, accounting for most brain malignancies”

“Glioblastoma is the most lethal cancer of the central nervous system, accounting for most brain malignancies,” says Prof. Satchi-Fainaro. “In a previous study, we identified a protein called P-Selectin, produced when glioblastoma cancer cells encounter microglia – cells of the brain’s immune system. We found that this protein is responsible for a failure in the microglia, causing them to support rather than attack the deadly cancer cells, helping the cancer spread. However, we identified the protein in tumors removed during surgery, but not in glioblastoma cells grown on 2D plastic petri dishes in our lab. The reason is that cancer, like all tissues, behaves very differently on a plastic surface than it does in the human body. Approximately 90% of all experimental drugs fail at the clinical stage because the success achieved in the lab is not reproduced in patients.”

Prof. Ronit Satchi-Fainaro

To address this problem, the research team led by Prof. Satchi-Fainaro and PhD student Lena Neufeld, recipient of the prestigious Dan David Fellowship, created the first 3D-bioprinted model of a glioblastoma tumor, which includes 3D cancer tissue surrounded by extracellular matrix, which communicates with its microenvironment via functional blood vessels.

Microscopic image of the 3D-bioprinted glioblastoma model. The bioprinted blood vessels are covered with endothelial cells (red) and pericytes (cyan). The blood vessels are surrounded with a brain-mimicking tissue composed of gliblastoma cells (blue) and the brain microenvironment cells (green). Different drugs or cells can be perfused through the 3D-bioprinted blood vessels to test their effect on the tumor tissue

“It’s not only the cancer cells…”

“It’s not only the cancer cells,” explains Prof. Satchi-Fainaro. “It’s also the cells of the microenvironment in the brain; the astrocytes, microglia and blood vessels connected to a microfluidic system – namely a system enabling us to deliver substances like blood cells and drugs to the tumor replica. Each model is printed in a bioreactor we have designed in the lab, using a hydrogel sampled and reproduced from the extracellular matrix taken from the patient, thereby simulating the tissue itself. The physical and mechanical properties of the brain are different from those of other organs, like the skin, breast, or bone. Breast tissue consists mostly of fat, bone tissue is mostly calcium; each tissue has its own properties, which affect the behavior of cancer cells and how they respond to medications. Growing all types of cancer on identical plastic surfaces is not an optimal simulation of the clinical setting.”

After successfully printing the 3D tumor, Prof. Satchi-Fainaro and her colleagues demonstrated that unlike cancer cells growing on petri dishes, the 3D-bioprinted model has the potential to be effective for rapid, robust, and reproducible prediction of the most suitable treatment for a specific patient.

“We proved that our 3D model is better suited for prediction of treatment efficacy, target discovery and drug development in three different ways.

First, we tested a substance that inhibited the protein we had recently discovered, P-Selectin, in glioblastoma cell cultures grown on 2D petri dishes, and found no difference in cell division and migration between the treated cells and the control cells which received no treatment. In contrast, in both animal models and in the 3D-bioprinted models, we were able to delay the growth and invasion of glioblastoma by blocking the P-Selectin protein.

This experiment showed us why potentially effective drugs rarely reach the clinic simply because they fail tests in 2D models, and vice versa: why drugs considered a phenomenal success in the lab, ultimately fail in clinical trials. In addition, collaborating with the lab of Dr. Asaf Madi of the Department of Pathology at TAU’s Faculty of Medicine, we conducted genetic sequencing of the cancer cells grown in the 3D-bioprinted model, and compared them to both cancer cells grown on 2D plastic and cancer cells taken from patients.

Thus, we demonstrated a much greater resemblance between the 3D-bioprinted tumors and patient-derived glioblastoma cells grown together with brain stromal cells in their natural environment. Through time, the cancer cells grown on plastic changed considerably, finally losing any resemblance to the cancer cells in the patient’s brain tumor sample.

The third proof was obtained by measuring the tumor growth rate. Glioblastoma is an aggressive disease partially because it is unpredictable: when the heterogeneous cancer cells are injected separately into model animals, the cancer will remain dormant in some, while in others, an active tumor will develop rapidly. This makes sense because we, as humans, can die peacefully of old age without ever knowing we have harbored such dormant tumors. On the dish in the lab, however, all tumors grow at the same rate and spread in the same rate. In our 3D-bioprinted tumor, the heterogeneity is maintained and development is similar to the broad spectrum that we see in patients or animal models.”

“…perhaps the most exciting aspect is finding novel druggable target proteins and genes in cancer cells…”

According to Prof. Satchi-Fainaro, this innovative approach will also enable the development of new drugs, as well as discovery of new drug targets – at a much faster rate than today. Hopefully, in the future, this technology will facilitate personalized medicine for patients.

“If we take a sample from a patient’s tissue, together with its extracellular matrix, we can 3D-bioprint from this sample 100 tiny tumors and test many different drugs in various combinations to discover the optimal treatment for this specific tumor. Alternately, we can test numerous compounds on a 3D-bioprinted tumor and decide which is most promising for further development and investment as a potential drug.

But perhaps the most exciting aspect is finding novel druggable target proteins and genes in cancer cells – a very difficult task when the tumor is inside the brain of a human patient or model animal. Our innovation gives us unprecedented access, with no time limits, to 3D tumors mimicking better the clinical scenario, enabling optimal investigation.”

Illustration for demonstration of 3D printing of a tumor in a brain Microenvironment according to a computed 3D model

The study was funded by the Morris Kahn Foundation, European Research Council (ERC), Israel Cancer Research Fund (ICRF), the Israel Cancer Association and Israel Science Foundation (ISF), and Check Point Software Technologies LTD.

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Recordings of the magnetic field from 9,000 years ago teach us about the magnetic field today

View west of the 1999 excavations, Stratum IIB,  Tel Tifdan/ Wadi Fidan. Photo courtesy of Thomas E. Levy

Tel Aviv University Research Links Archaeology, Physics, and Geophysics

  • Burnt archaeological flints enable us to determine the strength of the Earth’s magnetic field during prehistoric periods.
  • Information about the magnetic field in antiquity helps us understand the magnetic field today. Researchers: “the current weakening of the field is a reversible trend; Seven thousand six hundred years ago, the strength of the magnetic field was even lower than today, but within approximately 600 years, it gained strength and again rose to high levels.”

International research by Tel Aviv University, the Istituto Nazionale di Geofisica e Vulcanologia, Rome, and the University of California San Diego uncovered findings regarding the magnetic field that prevailed in the Middle East between approximately 10,000 and 8,000 years ago. Researchers examined pottery and burnt flints from archaeological sites in Jordan, on which the magnetic field during that time period was recorded. Information about the magnetic field during prehistoric times can affect our understanding of the magnetic field today, which has been showing a weakening trend that has been cause for concern among climate and environmental researchers.

The research was conducted under the leadership of Prof. Erez Ben-Yosef of the Jacob M. Alkow Department of Archaeology and Ancient Near Eastern Cultures at Tel Aviv University and Prof. Lisa Tauxe, head of the Paleomagnetic Laboratory at the Scripps Institution of Oceanography, in collaboration with other researchers from the University of California at San Diego, Rome and Jordan. The article was published in the journal PNAS.

Prof. Erez Ben-Yosef
Photo courtesy of Yoram Reshef

“Albert Einstein characterized the planet’s magnetic field as one of the five greatest mysteries of modern physics…”

Prof. Ben-Yosef explains, “Albert Einstein characterized the planet’s magnetic field as one of the five greatest mysteries of modern physics. As of now, we know a number of basic facts about it: The magnetic field is generated by processes that take place below a depth of approximately 3,000 km beneath the surface of the planet (for the sake of comparison, the deepest human drilling has reached a depth of only 20 km); it protects the planet from the continued bombardment by cosmic radiation and thus allows life as we know it to exist; it is volatile and its strength and direction are constantly shifting, and it is connected to various phenomena in the atmosphere and the planet’s ecological system, including – possibly – having a certain impact on climate. Nevertheless, the magnetic field’s essence and origins have remained largely unresolved. In our research, we sought to open a peephole into this great riddle.”

The researchers explain that instruments for measuring the strength of the Earth’s magnetic field were first invented only approximately 200 years ago. In order to examine the history of the field during earlier periods, science is helped by archaeological and geological materials that recorded the properties of the field when they were heated to high temperatures. The magnetic information remains “frozen” (forever or until another heating event) within tiny crystals of ferromagnetic minerals, from which it can be extracted using a series of experiments in the magnetics laboratory. Basalt from volcanic eruptions or ceramics fired in a kiln are frequent materials used for these types of experiments. The great advantage in using archaeological materials as opposed to geological is the time resolution: While in geology dating is on the scale of thousands years at best, in archaeology the artifacts and the magnetic field that they have recorded can be dated at a resolution of hundreds and sometimes even tens of years (and in specific cases, such as a known destruction event, even give an exact date). The obvious disadvantage of archaeology is the young age of the relevant artifacts: Ceramics, which have been used for this purpose up until now, were only invented 8,500 years ago.

Burnt flints and ceramics used to reconstruct the strength of the ancient geomagnetic field
(https://doi.org/10.1073/pnas.2100995118)

The current study is based on materials from four archaeological sites in Wadi Feinan (Jordan), which have been dated (using carbon-14) to the Neolithic period – approximately 10,000 to 8,000 years ago – some of which predate the invention of ceramics. Researchers examined the magnetic field that was recorded in 129 items found in these excavations, and this time, burnt flint tools were added to the ceramic shards.  Prof. Ben-Yosef: “This is the first time that burnt flints from prehistoric sites are being used to reconstruct the magnetic field from their time period. About a year ago, groundbreaking research at the Hebrew University was published, showing the feasibility of working with such materials, and we took that one step forward, extracting geomagnetic information from tightly dated burned flint. Working with this material extends the research possibilities tens of thousands of years back, as humans used flint tools for a very long period of time prior to the invention of ceramics. Additionally, after enough information is collected about the changes in the geomagnetic field over the course of time, we will be able to use it in order to date archaeological remains”.

Wadi Fidan 61 Pottery Neolithic.
Photo courtesy of Thomas E. Levy

An additional and important finding of this study is the strength of the magnetic field during the time period that was examined. The archaeological artifacts demonstrated that at a certain stage during the Neolithic period, the field became very weak (among the weakest values ever recorded for the last 10,000 years), but recovered and strengthened within a relatively short amount of time. According to Prof. Tauxe, this finding is significant for us today: “In our time, since measurements began less than 200 years ago, we have seen a continuous decrease in the field’s strength. This fact gives rise to a concern that we could completely lose the magnetic field that protects us against cosmic radiation and therefore, is essential to the existence of life on Earth. The findings of our study can be reassuring: This has already happened in the past. Approximately 7,600 years ago, the strength of the magnetic field was even lower than today, but within approximately 600 years, it gained strength and again rose to high levels.”

The research was carried out with the support of the US-Israel Binational Science Foundation, which encourages academic collaborations between universities in Israel and in the US. The researchers note that in this case, the collaboration was particularly essential to the success of the study because it is based on a tight integration of methods from the fields of archaeology and geophysics, and the insights that were obtained are notably relevant to both of these disciplines.

Link to the article:

https://doi.org/10.1073/pnas.2100995118

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The Silent Prophets

TAU researchers prove that silent mutations can predict development of cancer cells.

Our genome, our complete set of genetic instructions, contains mutations that can change the sequence of amino acids in the coded proteins. Since these proteins are responsible for the various cell mechanisms, such mutations are involved in turning healthy cells into cancer cells. In contrast, there are so-called ‘silent mutations’ that don’t change the sequence of amino acids in proteins. In recent years, it has been shown that silent mutations, both in and out of the cell’s genetic coding region, can affect gene expression, and may be associated with the development and spread of cancer cells. However, the question of whether silent mutations can help identify cancer types or predict patients’ chances of survival has never before been investigated with quantitative tools. Researchers from TAU’s Department of Biomedical Engineering and the Zimin Institute for Engineering Solutions Advancing Better Lives have been able to predict both the type of cancer and patients’ survival probability based on silent mutations in cancer genomes – a proof of concept that may well save lives in the future.

Predictive Power Similar to That of ‘Ordinary’ Mutations.

The groundbreaking study, led by Prof. Tamir Tuller and research student Tal Gutman, is based on about three million mutations from cancer genomes of 9,915 patients. The researchers attempted to identify the type of cancer and predict survival probability 10 years after the initial diagnosis – on the basis of silent mutations alone. They found that the predictive power of silent mutations is often similar to that of ‘ordinary’, non-silent mutations.

In addition, they discovered that by combining information from silent and non-silent mutations classification could be improved for 68% of the cancer types, and the best survival estimations could be obtained up to nine years after diagnosis. In some types of cancer classification was improved by up to 17%, while prognosis was improved by up to 5%. The findings of the study were recently published in NPJ Genomic Medicine.

Silent, Yet Making Noise

“‘Silent mutations’ have been ignored by researchers for many years,” explains Prof. Tuller. “In our study, about 10,000 cancer genomes of every type were analyzed, demonstrating for the first time that silent mutations do have diagnostic value – for identifying the type of cancer, as well as prognostic value – for predicting how long the patient is likely to survive.”

According to the professor, the cell’s genetic material holds two types of information: first, the sequence of amino acids to be produced, and second, when and how much to produce of each protein – namely regulation of the production process. “Even if they don’t change the structure of the protein, silent mutations can influence the process of protein production (gene expression), which is just as important. If a cell prodces much smaller quantities of a certain protein – it’s almost as though the protein has been eliminated altogether.”

“Another important aspect, which can also be affected by silent mutations, is the protein’s 3D folding, which impacts its functions: Proteins are long molecules usually consisting of many hundreds of amino acids, and their folding process begins when they are produced in the ribosome. Folding can be affected by the rate at which the protein is produced, which may in turn be affected by silent mutations.”

“Also, in some cases, silent mutations can impact a process called splicing, in which pieces of the genetic material are cut and rearranged to create the final sequence in the protein.”

Apparently, silent mutations can actually make a lot of noise, and Prof. Tuller and his colleagues were able to quantify their impact for the first time.

Saving as Many Lives as Possible

To test their hypothesis and quantify the effect of the silent mutations, the researchers used public genetic information about cancer genomes from the NIH in the USA. Applying machine learning techniques to this data, the team obtained predictions of the type of cancer and prognoses for patients’ survival – based on silent mutations alone. They then compared their results with real data from the database.

“The results of our study have several important implications,” says Prof. Tuller. “First of all, there is no doubt that by using silent mutations we can improve existing diagnostic and prognostic models. It should be noted that even a 17% improvement is very significant, because there are real people behind these numbers – sometimes even ourselves or our loved ones.”

“Doctors discovering metastases would like to know where they came from and how the disease has developed, in order to prescribe the best treatment. If, hypothetically, instead of giving wrong diagnoses and prognostics to five out of ten cancer patients, they only make mistakes in four out of ten cases, millions of lives may ultimately be saved. In addition, our results indicate that in many cases silent mutations can by themselves provide predictive power that is similar to that of non-silent mutations. These results are especially significant for a range of technologies currently under development, striving to diagnose cancer types based on DNA from malignant sources identified in simple blood tests. Since most of our DNA does not code for proteins, we may assume that most cancer DNA obtained from blood samples will contain silent mutations.”

The new study has implications for all areas of oncological research and treatment. Following this proof of concept, the researchers intend to establish a startup with Sanara Ventures, focusing on silent mutations as a diagnostic and prognostic tool.

Featured image: Prof. Tamir Tuller (Photo: Rafael Ben Menashe)

Israel-Indian academic ties boosted by visit of Indian Minister of External Affairs

(Left to right): President of Ben-Gurion University of the Negev, Prof. Daniel Chamovitz, Minister of External Affairs of India ,
Dr S. Jaishankar, and President of Tel Aviv University, Prof. Ariel Porat.

All photos by Shlomi Amsalem, Courtesy of Tel Aviv University

Meeting of Israeli university presidents and senior leadership with Dr S. Jaishankar, Minister of External Affairs of India.

Tel Aviv University hosted a meeting of Israeli university presidents with Dr S. Jaishankar, Minister of External Affairs of India. The Minister met with university presidents and senior leadership from Tel Aviv University, Hebrew University of Jerusalem, the Technion, Ben Gurion University, Haifa University and Bar Ilan University to discuss opportunities for expanding and deepening academic ties between the two countries. The Minister also met with a group of Indian students studying in Israel to hear about their experiences and suggestions for how to expand student mobility.

The Minister noted that universities play a significant role in strengthening bilateral relations and whilst there has been increased cooperation in the higher education field in recent years, there is much potential to boost ties in many fields, including technology and innovation. Currently there are around 1,000 Indian students studying in Israel, around half of them post-doctoral students. The Minister said that India is “committed to finding new ways to expand our relationship”, and “the challenge before us is how to scale it up and shift it to the next gear”.

Professor Ariel Porat, President of Tel Aviv University, noted the significance of the Minister’s visit in the context of the upcoming 30th anniversary of diplomatic relations and growing ties between the two countries. Professor Porat stressed that “TAU sees India as a strategic priority and we see great potential in expanding our partnerships with leading academic institutions and industry in India”. Professor Daniel Chamovitz, President of Ben Gurion University said “The strong academic collaboration between India and Israel is built on common values which facilitates the personal interactions”. The Israeli university leaders called for the establishment of more bilateral mechanisms to support joint research and student mobility.

Roohi Chaudry, PhD student in the field of cancer biophysics at TAU, reflecting on her experiences studying in Israel said “studying at TAU and Israel has helped me to gain insight into so many diverse cultures and take a giant leap out of my comfort zone to unravel endless opportunities. The well-equipped research labs with world class infrastructure and the most advanced innovative learning techniques assisted in reinforcing my desire to take up research as my line of work”. She applauded the Minister’s visit and called for the “more student exchanges in the future which will prove to be a testimony in strengthening Indo-Israel relations”.

Meeting of Indian students studying in Israel with Dr S. Jaishankar, Minister of External Affairs of India.

 

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For the 1st time at an Israeli university: Air and Space Power Center

Tel Aviv University and the Israeli Air Force establish a joint center that will harness the world of civilian research and knowledge to advance various areas related to policymaking and strategic thinking on issues of air and space.

On Thursday Dec. 30, Tel Aviv University and the Israeli Air Force launched the Air and Space Power Center at TAU, named the Elrom Center. The new Center, which is the first of its kind in Israel, will harness the world of research and knowledge to advance various areas related to air and space power in Israel.

The ceremony, held at TAU, was led by TAU President Prof. Ariel Porat, in the presence of Air Force Commander Aluf Amikam Norkin.

At the ceremony Prof. Porat and Aluf Norkin signed a joint document emphasizing that “a framework has been formed for multidisciplinary research promoting theoretical and practical knowledge on air and space power, as well as fruitful ties between academia and a range of other sectors, including industry, nonprofits and organizations, government agencies, and Israel’s security forces, to develop education and cultivate a cadre of future researchers in this important field.”

The new Center adds one more layer to TAU’s vision of advancing groundbreaking multidisciplinary research that brings together the university’s finest researchers, the hi-tech industry, and the community. The Center joins several other multidisciplinary centers established at TAU over the past year, including the Center for Combating Pandemics, the Center for Climate Change Action, the Center for Artificial Intelligence and Data Science, and the Center for Aging.

The center is also an important addition to the vision of the Israeli Air Force – to establish a national research and academic foundation in the field of Air and Space Power, in order to harness scientific knowledge for the benefit of the Air Force, encouraging creative and critical thinking and accelerating the incorporation of innovation into world views of the Air Force.

The new Center will be headed by Prof. Eviatar Matania of the Blavatnik Interdisciplinary Cyber Research Center, formerly founding Head of the Israel National Cyber Bureau and currently Head of the International Cyber Politics & Government Program at TAU. Combining theoretical and applied research, it will operate within the Gordon Faculty of Social Sciences but will also involve researchers from Engineering, Exact Sciences, and Medicine, and serve as a foundation for advancing multidisciplinary research on air and space.

In this context the Center will develop a cadre of future researchers and establish systematic academic activity in this area in Israel. It will encourage students to specialize in air & space power – both students who belong to nonprofits and organizations, government agencies and the security forces, and students looking to develop a career in industry in these important fields.

In the Israeli Air Force, the Air and Space Power Center will support the development of a foundation of academic knowledge. The academic research carried out at the Center can help in the development and adaptation of the Air Force’s operational concepts, combat doctrines, and power- building processes. Methodological tools for professional, abstract, and practical thinking developed by the Center’s researchers will also be beneficial. In the foreseeable future the Center will serve as a hub for international research collaboration with academic institutions, research institutes and air forces around the world.

Aluf Amikam Norkin & Prof. Ariel Porat (Photo credit: Israel Hadari.)

 TAU President Prof. Ariel Porat: “The field of Air and Space Power is important and promising, both socially and scientifically. Many researchers at TAU address this subject from different angles, and the new Center will contribute a great deal to the advancement and development of both research and education in this area. Tel Aviv University conducts many research collaborations with industry and public organizations, which upgrade our research and make it more relevant. At the newly established Center, many more participants from industry and academia, both in Israel and worldwide, will become involved, advancing Air and Space Power research.”

 Israeli Air Force Commander, Aluf Amikam Norkin: “Today we are groundbreaking pioneers in a vast range of operational issues which have grown in response to the challenges of our Middle-Eastern neighborhood. Thus, together with the IDF’s intelligence operations, air power has become the main answer to the country’s security challenges. Fighting terrorism from the air, air supremacy, remotely piloted aircraft, the most advanced air defense in the world, and three F-35 squadrons – are only some of the aspects in which the Israeli Air Force, together with Israel’s defense industries, are leaders and pioneers.

Ben Gurion’s vision, and his understanding that ‘the air is a new kingdom we must conquer’, has become a reality. But we must not rest on our laurels. Only in-depth investigation of ongoing operations will keep us sharp and ready. Yet as we look toward the coming decades, we need more than excellent inquiry. We must expand our activities into the academic arena, to include research methods developed in Israeli academia, at Tel Aviv University. We must set in motion both military and civilian research on air and space power, that will open new horizons to which we may aspire.

The establishment of the Air and Space Power Center, bringing together experts from academia and the Air Force, transforms a vision into reality. This is a real need arising from the constantly rising complexity of the battlefield and operational challenges, requiring ever greater and deeper military knowledge – in order to ensure the position of the Israeli Air Force as one of the leading forces in the world.”

Featured image: (left to right) Prof. Eviatar Matania, Prof. Ariel Porat, Dafna Meitar-Nechmad & Aluf Amikam Norkin (Photo credit: Israel Hadari.)

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