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Tag: Medicine

Nicotine Testing of Children Curbs Parents’ Smoking

Written by AUFTAU on . Posted in Newsroom.

70% of children of smokers suffer from secondhand smoking.

Warnings against the dangers of smoking can be read on every cigarette box and in every advertisement for smoking brands. Those who smoke endanger themselves and also those around them, who inevitably become passive smokers. This way, parents who smoke harm the health of their own children. A first-of-its-kind study in Israel by researchers from the Sackler Medical School of Tel Aviv University uncovers alarming data about secondhand smoking by children of smokers: According to the study, nicotine residues were found in the hair samples of 7 out of 10 children who participated. The research team found that parental behavior may be changed through regular monitoring of children’s exposure.

Nicotine Residue in Children’s Hair

The study was conducted under the leadership of a team of experts from the Tel Aviv University School of Medicine headed by Prof. Leah (Laura) Rosen of the School of Public Health together with researchers Dr. Vicki Myers, Prof. Nurit Guttman, Ms. Nili Brown, Prof. Mati Berkovitch, and Dr. Michal Bitan. Prof. David Zucker of the Hebrew University of Jerusalem and Dr. Anna Rule of Johns Hopkins University in the US also participated in the study. The study was published in the prestigious journal, Nicotine & Tobacco Research.

In the study, the researchers sought to examine whether raising awareness of children’s exposure by providing objective feedback might change the parents’ behavior and child exposure. 140 Israeli families participated in the study, parents of children up to age 8, at least one parent being a smoker. The smoking average per household was 15 cigarettes per day, where one third of the respondents reported that they smoke inside the home, and one third said that they smoke on the terrace but not inside the home.

First, researchers tested children’s level of exposure via a biomarker, nicotine in hair, which indicates cumulative exposure to tobacco smoke. The researchers took hair samples from the children and tested the nicotine levels in each sample (it is important to note that the test was for nicotine that became an integral part of the strand of hair and not just outside precipitate.) The findings were very concerning: Nicotine residue was found in the hair of 70% of the children tested. Only 29.7% of the children tested did not show nicotine residue in their hair samples. 

The researchers divided the families into two groups: one group underwent comprehensive instruction about the effects and dangers of exposure to smoking, including feedback and information about the test results. The group was also given tools to protect their children from exposure to cigarette smoke and a recommendation to keep their home and car smoke-free. The second group received feedback about nicotine levels in the children’s hair after six months, at the end of the study.

Limiting Children’s Exposure

Six months after the start of the study, the researchers conducted additional nicotine tests on the children’s hair, and one could already see a significant improvement in the data: Among the group that received comprehensive training, the percentage of children whose hair samples contained nicotine decreased from 66% to 53%, whereas in the second group (which did not receive training at the start of the study), the percentage of children whose hair samples contained nicotine decreased from 74% to 49%. Thus, just testing the children, without even informing families of the results, was enough to seemingly change parents’ behaviors.

The researchers theorize that the knowledge that the children were tested for tobacco smoke exposure, and that additional testing was planned at six months, resulted in the parents changing their behavior and reducing the children’s exposure. As a result of the study’s findings, the researchers recommend considering conducting such testing to measure exposure on a routine basis among young children in Israel.

The Right to Breathe Smoke-Free Air

Prof. Leah Rosen: “To our great dismay, according to the Ministry of Health’s data, approximately 60% of small children in Israel are exposed to secondhand smoke and its harmful effects. Based on the study’s findings, we believe that conducting nicotine testing – in the hair, urine, or using other testing methods – for every young child in Israel, may change parents’ perceptions about exposing their children to tobacco smoke. Changing this perception can also result in changing behavior, exposure levels, and even social norms regarding passive exposure to smoking – both exposure of children as well as exposure of adults.”

“We call upon smokers to avoid smoking anyplace where non-smokers and in particular, at-risk populations, including children, pregnant women, elderly, and those who are ill, could be exposed. Non-smokers must understand that there is genuine risk in exposure to tobacco smoke, and they must insist upon their right and the right of their children and family members to breathe air that is smoke-free everywhere. Of course, the government has a central role in enforcing laws pertaining to smoking in public places and continuing to enact laws to protect the individual everywhere from exposure to secondhand smoke.” 

The Silent Prophets

Written by AUFTAU on . Posted in Newsroom, Press release.

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)

Want to Fall in Love? Step Outside in The Sun

Written by AUFTAU on . Posted in Newsroom.

Exposure to ultraviolet radiation from sunlight enhances romantic passion in humans.

Any Tel Avivian will tell you that the perfect place for a first date is at the beach. Now, we have the science to support that claim. Researchers at Tel Aviv University have found that exposure to ultraviolet radiation from sunlight enhances romantic passion in humans. In the study, men and women were exposed to UVB (ultraviolet radiation type B) under controlled conditions, and the findings were unequivocal: increased levels of romantic passion in both genders.

Sun + Skin = Love

The study revealed that exposure to sunlight affects the regulation of the endocrine system responsible for the release of sexual hormones in humans. The discovery may lead to practical applications down the line, such as UVB treatments for sexual hormone disorders.

In animal models, the effect was dramatic: the females’ hormone levels rose significantly, enlarging their ovaries and prolonging their mating season; the attraction between males and females increased; and both were more willing to engage in sexual intercourse.

The researchers repeated the experiment on the animal model, this time removing from the skin a protein called p53, which identifies DNA damage and activates pigmentation during exposure to sunlight as protection against its adverse effects. The removal of the protein eliminated the effect of UVB exposure on the animals’ sexual behavior, convincing the researchers that exposure to radiation through the skin was the cause of the observed hormonal, physiological and behavioral changes, and that the protective system is also responsible for the regulation of sexuality.

Furless Humans and Sun Exposure

In the 32 human subjects of the study, all treated with UVB phototherapy at the Tel Aviv Sourasky (Ichilov) and Assuta Medical Centers, both genders exhibited a rise in romantic passion, and males also noted an increase in levels of aggression.

Similar results were found when the subjects were asked to avoid sunlight for two days, and then tan themselves for approximately 25 minutes. Blood tests revealed that exposure to sunlight resulted in a higher release of hormones like testosterone compared to one day before exposure. A rise in testosterone in males during the summer was also found in analyses of data from the Israeli health maintenance organizations Clalit and Maccabi Health Services.

 

Prof. Carmit Levy (on the left) & PhD student Roma Parikh.

The new discovery from TAU may lead to future practical applications, such as UVB treatments for sexual hormone disorders. The breakthrough opens up for further discoveries in basic science, “As humans, we have no fur, and our skin is thus directly exposed to sunlight. We are only beginning to understand what this exposure does to us, and the key roles it might play in various physiological and behavioral processes. It’s only the tip of the iceberg,” says Prof. Carmit Levy from the Department of Human Molecular Genetics and Biochemistry at the Sackler Faculty of Medicine.

The study was led by PhD student Roma Parikh and Ashchar Sorek from the laboratory of Prof. Levy. UVB phototherapy was administered to the subjects at the Tel Aviv Sourasky (Ichilov) and Assuta Medical Centers. The groundbreaking discovery was published as a cover story in the prestigious scientific journal Cell Reports. 

First 3D-bioprinting of entire active tumor

Written by AUFTAU on . Posted in Newsroom, Press release.

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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New Warning Sign for Breast Cancer

Written by AUFTAU on . Posted in Newsroom.

TAU-led research lays groundwork for preventive treatment that may save millions of lives.

A team led by Tel Aviv University identified a new indicator of metastatic breast cancer, laying the groundwork for preventive treatment that could save millions of lives.

Metastatic breast cancer, also known as Stage 4 breast cancer, occurs when cancer has spread, or “metastasized,” to other parts of the body. Mortality from breast cancer is almost exclusively a result of tumor metastasis, and lungs are one of the main metastatic sites. The five-year survival rate for women with metastatic breast cancer is estimated at 28%.

Investigating The “Black Box” of Breast Cancer 

“Breast cancer patients, as well as patients with many other types of cancer, do not die from the primary tumor, but from distant metastases which have developed, sometimes after years, in essential organs such as the lungs and brain,” said the study’s lead researcher, Prof. Neta Erez, Chair of the Department of Pathology at TAU’s Sackler Faculty of Medicine. “Understanding the body’s preparation for the reception of metastases at an early stage may save millions of lives.”

The researchers explain that metastases can appear several years after the initial cases are treated. Today, methods used for follow-up screening identify metastases only when they are quite large–when the disease is at an advanced stage and unlikely to be cured.

For this reason, Erez’s research group is investigating the black box—the time period between apparent recovery and the appearance of metastases to understand the metastatic process and to find ways of blocking it in early stages. Their research in recent years has revealed that certain tissues, in organs where the metastases are set to arrive, “prepare the area” for reception and produce a hospitable environment for them, a long time before the appearance of the metastases themselves. In the present study, the research team searched for signs of these changes, which may be used in the future to identify the start of the process that predicts metastases. The researchers identified these changes in the area known as “the micro-environment” of the tumor, and specifically in connective tissue known as fibroblasts which are found in the lungs among other places. 

“In a normal situation, fibroblasts play a central role in healing wounds and injury to the lungs, but recent studies revealed that cancer is successful in recruiting them and causing them to produce a supportive environment for it,” said Erez.

What is Happening in the Micro-environment of the Metastases?

The researchers compared genes sequenced from healthy lungs, from lungs with micro-metastases (very small metastases which cannot be identified using existing clinical tools) and from lungs with large metastases, in a state of advanced disease.

By identifying and comparing the respective development in the three different types of sample tissues, the researchers succeeded, for the first time, in characterizing the process that occurs in the micro-environment of the metastases. The findings provide valuable understanding about how cancer cells grow, which can then be leveraged for detection by existing imaging methods and treated to prevent metastasis.

The study’s leading research team from Erez’s laboratory included Dr. Ophir Shani and Dr. Yael Raz along with additional researchers from Tel Aviv University, Sheba Medical Center at Tel HaShomer, Tel Aviv Sourasky Medical Center (Ichilov Hospital), and the Weizmann Institute of Science. The findings were published in the prestigious peer-reviewed journal eLife.  

Featured image: Prof. Neta Erez (Photo: Michal Kidron)

COVID-19 Immunity Varies Among Genders and Age Groups

Written by AUFTAU on . Posted in Newsroom.

TAU researchers contribute a new piece to the puzzle on the effectiveness of COVID-19 vaccination.

As experts continue to learn more about immune responses to COVID-19 and the effectiveness of vaccines, researchers from Tel Aviv University have contributed a new piece to the puzzle. A joint study conducted by researchers from TAU and the Shamir Medical Center (Assaf Harofe) indicates that the level of antibodies changes according to age groups, gender, symptoms, and time elapsed since vaccination. The findings are the latest from the researchers in a series of studies aimed at providing reliable measures on the effectiveness of COVID-19 vaccination.

The new study examined the level of antibodies in over 26,000 blood samples taken from COVID-19 convalescents, as well as vaccinated and unvaccinated individuals.

In vaccinated individuals, the researchers found differences between 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, and may be related to changes in levels of testosterone and the effect on the immune system.

In young adults, a high concentration of antibodies generally signals a strong healthy functioning immune response, while in older demographics it typically indicates overreaction of the immune system associated with severe illness. 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. The findings further validate existing evidence that, depending on age, higher antibody count isn’t necessarily equivalent to higher rates of recovery.

Furthermore, the study found that the immune response of vaccinated individuals (after two doses) is much stronger than that of people who have recovered from COVID-19. The findings show that vaccinated individuals have four times the level of antibodies compared to convalescents.

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. The study was published in Medrxiv. 

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

Written by AUFTAU on . Posted in Newsroom, Press release.

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

Written by AUFTAU on . Posted in Newsroom, Press release.

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 nanotech from TAU produces “healthy” electric current from the human body itself

Written by AUFTAU on . Posted in Newsroom.

Approach allows for the charging of cardiac pacemakers using only the heartbeat, eliminating the need for batteries

A new nanotechnology development from an international research team led by Tel Aviv University researchers will make it possible to generate electric currents and voltage within the human body itself through the activation of various organs using mechanical force. The development involves a new and very strong biological material, similar to collagen, which is non-toxic and causes no harm to the body’s tissues.

The researchers believe that this new nanotechnology has many potential applications in medicine, including harvesting clean energy to operate pacemakers and other devices implanted in the body through the body’s natural movements, eliminating the need for batteries and the surgery required to replace them.

The study was led by Professor Ehud Gazit of TAU’s Shmunis School of Biomedicine and Cancer Research at the George S. Wise Faculty of Life Sciences, the Department of Materials Science and Engineering at the Fleischman Faculty of Engineering and the Center for Nanoscience and Nanotechnology, along with his lab team, Dr. Santu Bera and Dr. Wei Ji.

Researchers from the Weizmann Institute and a number of research institutes in Ireland, China and Australia also took part in the study, which was published in Nature Communications.

“Collagen is the most prevalent protein in the human body, constituting about 30% of all of the proteins in our body,” Professor Gazit, who is also Founding Director of TAU’s Blavatnik Center for Drug Discovery, explains. “It is a biological material with a helical structure and a variety of important physical properties, such as mechanical strength and flexibility, which are useful in many applications. However, because the collagen molecule itself is large and complex, researchers have long been looking for a minimalistic, short and simple molecule that is based on collagen and exhibits similar properties.

“About a year and a half ago our group published a study in which we used nanotechnological means to engineer a new biological material that meets these requirements,” Professor Gazit continues. “It is a tripeptide — a very short molecule called Hyp-Phe-Phe consisting of only three amino acids — capable of a simple process of self-assembly of forming a collagen-like helical structure that is flexible and boasts a strength similar to that of the metal titanium.

“In the present study, we sought to examine whether the new material we developed bears piezoelectricity, another feature that characterizes collagen. Piezoelectricity is the ability of a material to generate electric currents and voltage as a result of the application of mechanical force, or vice versa, to create a mechanical force as the result of exposure to an electric field.”

The researchers created nanometric structures of the engineered material, and with the help of advanced nanotechnology tools applied mechanical pressure on them. The experiment revealed that the material does indeed produce electric currents and voltage as a result of the pressure.

Moreover, tiny structures of mere hundreds of nanometers demonstrated one of the highest levels of piezoelectric ability ever discovered, comparable or superior to that of the piezoelectric materials commonly found in today’s market, most of which contain lead and are unsuitable for medical applications.

According to the researchers, the discovery of piezoelectricity of this magnitude in a nanometric material is of great significance, as it demonstrates the ability of the engineered material to serve as a kind of tiny motor for very small devices. Next, the researchers plan to apply crystallography and computational quantum mechanical methods (density functional theory) in order to gain an in-depth understanding of the material’s piezoelectric behavior and thereby enable the accurate engineering of crystals for the building of biomedical devices.

“Most of the piezoelectric materials that we know of today are toxic lead-based materials, or polymers, meaning they are not environmentally and human body-friendly,” Professor Gazit says. “Our new material, however, is completely biological and suitable for uses within the body.

“For example, a device made from this material may replace a battery that supplies energy to implants like pacemakers, though it should be replaced from time to time. Body movements like heartbeats, jaw movements, bowel movements, or any other movement that occurs in the body on a regular basis will charge the device with electricity, which will continuously activate the implant.”

His current focus is on the development of medical devices, but Professor Gazit emphasizes that “environmentally friendly piezoelectric materials, such as the one we have developed, have tremendous potential in a wide range of areas because they produce green energy using mechanical force that is being used anyway. For example, a car driving down the street can turn on the streetlights. These materials may also replace lead-containing piezoelectric materials that are currently in widespread use, but that raise concerns about the leakage of toxic metal into the environment.”

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

Written by AUFTAU on . Posted in Newsroom.

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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