Tag: Research

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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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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Introducing the world’s thinnest technology – only two atoms thick

Technological breakthrough from Tel Aviv University

The research team
  • The new technology, enabling the storage of information in the thinnest unit known to science, is expected to improve future electronic devices in terms of density, speed, and efficiency.

  • The allowed quantum-mechanical electron tunneling through the atomically thin film may boost the information reading process much beyond current technologies.

  • The technology involves laterally sliding one-atom-thick layers of boron and nitrogen one over the other – a new way to switch electric polarization on/off.

A scientific breakthrough: Researchers from Tel Aviv University have engineered the world’s tiniest technology, with a thickness of only two atoms. According to the researchers, the new technology proposes a way for storing electric information in the thinnest unit known to science, in one of the most stable and inert materials in nature. The allowed quantum-mechanical electron tunneling through the atomically thin film may boost the information reading process much beyond current technologies.

The research was performed by scientists from the Raymond and Beverly Sackler School of Physics and Astronomy and Raymond and Beverly Sackler School of Chemistry.  The group includes Maayan Vizner Stern, Yuval Waschitz, Dr. Wei Cao, Dr. Iftach Nevo, Prof. Eran Sela, Prof. Michael Urbakh, Prof. Oded Hod, and Dr. Moshe Ben Shalom. The work is now published in Science magazine.

“Our research stems from curiosity about the behavior of atoms and electrons in solid materials, which has generated many of the technologies supporting our modern way of life,” says Dr. Ben Shalom. “We (and many other scientists) try to understand, predict, and even control the fascinating properties of these particles as they condense into an ordered structure that we call a crystal. At the heart of the computer, for example, lies a tiny crystalline device designed to switch between two states indicating   different responses – “yes” or “no”, “up” or “down” etc. Without this dichotomy – it is not possible to encode and process information. The practical challenge is to find a mechanism that would enable switching in a small, fast, and inexpensive device.

Current state-of-the-art devices consist of tiny crystals that contain only about a million atoms (about a hundred atoms in height, width, and thickness) so that a million of these devices can be squeezed about a million times into the area of one coin, with each device switching at a speed of about a million times per second.

Following the technological breakthrough, the researchers were able, for the first time, to reduce the thickness of the crystalline devices to two atoms only. Dr. Ben Shalom emphasizes that such a thin structure enables memories based on the quantum ability of electrons to hop quickly and efficiently through barriers that are just several atoms thick. Thus, it may significantly improve electronic devices in terms of speed, density, and energy consumption.

In the study, the researchers used a two-dimensional material: one-atom-thick layers of boron and nitrogen, arranged in a repetitive hexagonal structure. In their experiment, they were able to break the symmetry of this crystal by artificially assembling two such layers. “In its natural three-dimensional state, this material is made up of a large number of layers placed on top of each other, with each layer rotated 180 degrees relative to its neighbors (antiparallel configuration)” says Dr. Ben Shalom. “In the lab, we were able to artificially stack the layers in a parallel configuration with no rotation, which hypothetically places atoms of the same kind in perfect overlap despite the strong repulsive force between them (resulting from their identical charges). In actual fact, however, the crystal prefers to slide one layer slightly in relation to the other, so that only half of each layer’s atoms are in perfect overlap, and those that do overlap are of opposite charges – while all others are located above or below an empty space – the center of the hexagon. In this artificial stacking configuration the layers are quite distinct from one another. For example, if in the top layer only the boron atoms overlap, in the bottom layer it’s the other way around.”

Dr. Ben Shalom also highlights the work of the theory team, who conducted numerous computer simulations “Together we established deep understanding of why the system’s electrons arrange themselves just as we had measured in the lab. Thanks to this fundamental understanding, we expect fascinating responses in other symmetry-broken layered systems as well,” he says.

Maayan Wizner Stern, the PhD student who led the study, explains: “The symmetry breaking we created in the laboratory, which does not exist in the natural crystal, forces the electric charge to reorganize itself between the layers and generate a tiny internal electrical polarization perpendicular to the layer plane. When we apply an external electric field in the opposite direction the system slides laterally to switch the polarization orientation. The switched polarization remains stable even when the external field is shut down. In this the system is similar to thick three-dimensional ferroelectric systems, which are widely used in technology today.”

“The ability to force a crystalline and electronic arrangement in such a thin system, with unique polarization and inversion properties resulting from the weak Van der Waals forces between the layers, is not limited to the boron and nitrogen crystal,” adds Dr. Ben Shalom. “We expect the same behaviors in many layered crystals with the right symmetry properties. The concept of interlayer sliding as an original and efficient way to control advanced electronic devices is very promising, and we have named it Slide-Tronics”.

Maayan Vizner Stern concludes: “We are excited about discovering what can happen in other states we force upon nature and predict that other structures that couple additional degrees of freedom are possible. We hope that miniaturization and flipping through sliding will improve today’s electronic devices, and moreover, allow other original ways of controlling information in future devices. In addition to computer devices, we expect that this technology will contribute to detectors, energy storage and conversion, interaction with light, etc. Our challenge, as we see it, is to discover more crystals with new and slippery degrees of freedom.”

The study was funded through support from the European Research Council (ERC starting grant), the Israel Science Foundation (ISF), and the Ministry of Science and Technology (MOST).

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A world first: Targeted delivery of therapeutic RNAs only to cancer cells, with no harm caused to healthy cells

Tel Aviv University’s Groundbreaking Technology:

The “door-to-door service” that delivers therapeutic RNA payloads directly to cancer cells and other diseased cells 

  • The groundbreaking technology may revolutionize the treatment of cancer and a wide range of diseases and medical conditions.

  • Researcher Prof. Peer: “Our development actually changes the world of therapeutic antibodies. Today we flood the body with antibodies that, although selective, also damage healthy cells. We have now removed the uninfected cells from the equation, and, via a simple injection, succeeded in targeting only the cells that are inflamed at that given moment.”

  • The study was published in the prestigious scientific journal Nature.

Tel Aviv University’s groundbreaking technology may revolutionize the treatment of cancer and a wide range of diseases and medical conditions. In the framework of this study, the researchers were able to create a new method of transporting RNA-based drugs to a subpopulation of immune cells involved in the inflammation process, and target the disease-inflamed cell without causing damage to other cells.

The study was led by Prof. Dan Peer, a global pioneer in the development of RNA-based therapeutic delivery. He is Tel Aviv University’s Vice President for Research and Development, head of the Center for Translational Medicine and a member of both the Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, and the Center for Nanoscience and Nanotechnology. The study was published in the prestigious scientific journal Nature.

Prof. Peer: “Our development actually changes the world of therapeutic antibodies. Today we flood the body with antibodies that, although selective, damage all the cells that express a specific receptor, regardless of their current form. We have now taken out of the equation healthy cells that can help us, that is, uninflamed cells, and via a simple injection into the bloodstream can silence, express or edit a particular gene exclusively in the cells that are inflamed at that given moment.”

As part of the study, Prof. Peer and his team were able to demonstrate this groundbreaking development in animal models of inflammatory bowel diseases such as Crohn’s disease and colitis, and improve all inflammatory symptoms, without performing any manipulation on about 85% of the immune system cells. Behind the innovative development stands a simple concept, targeting to a specific receptor conformation.

“On every cell envelope in the body, that is, on the cell membrane, there are receptors that select which substances enter the cell,” explains Prof. Peer. “If we want to inject a drug, we have to adapt it to the specific receptors on the target cells, otherwise it will circulate in the bloodstream and do nothing. But some of these receptors are dynamic – they change shape on the membrane according to external or internal signals. We are the first in the world to succeed in creating a drug delivery system that knows how to bind to receptors only in a certain situation, and to skip over the other identical cells, that is, to deliver the drug exclusively to cells that are currently relevant to the disease.”

Previously, Prof. Peer and his team developed delivery systems based on fatty nanoparticles – the most advanced system of its kind; this system has already received clinical approval for the delivery of RNA-based drugs to cells. Now, they are trying to make the delivery system even more selective.

According to Prof. Peer, the new breakthrough has possible implications for a wide range of diseases and medical conditions. “Our development has implications for many types of blood cancers and various types of solid cancers, different inflammatory diseases, and viral diseases such as the coronavirus. We now know how to wrap RNA in fat-based particles so that it binds to specific receptors on target cells,” he says. “But the target cells are constantly changing. They switch from ‘binding’ to ‘non-binding’ mode in accordance with the circumstances. If we get a cut, for example, not all of our immune system cells go into a ‘binding’ state, because we do not need them all in order to treat a small incision. That is why we have developed a unified protein that knows how to bind only to the active state of the receptors of the immune system cells. We tested the protein we developed in animal models of inflammatory bowel disease, both acute and chronic.”

Prof. Peer adds, “We were able to organize the delivery system in such a way that we target to only 14.9% of the cells that were involved in the inflammatory condition of the disease, without adversely affecting the other, non-involved, cells, which are actually completely healthy cells. Through specific binding to the cell sub-population, while delivering the RNA payload we were able to improve all indices of inflammation, from the animal’s weight to pro-inflammatory cytokines. We compared our results with those of antibodies that are currently on the market for Crohn’s and colitis patients, and found that our results were the same or better, without causing most of the side effects that accompany the introduction of antibodies into the entire cell population. In other words, we were able to deliver the drug ‘door-to-door,’ directly to the diseased cells.”

The study was led by Prof. Peer, together with Dr. Niels Dammes, a postdoctoral fellow from the Netherlands, with the collaboration of Dr. Srinivas Ramishetti, Dr. Meir Goldsmith and Dr. Nuphar Veiga, from Prof. Dan Peer’s lab. Professors Jason Darling and Alan Packard of Harvard University in the United States also participated. The study was funded by the European Union, in the framework of the European Research Council (ERC).

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