Technology-driven treatment found to be as effective as psychiatric medications
Research
Apr 16th, 2023
Drug-Free Alternative for People with Social Anxiety
- Social Sciences
- Psychology
A new clinical trial conducted at Tel Aviv University has demonstrated an effective technology-driven alternative to psychiatric medications for people with social anxiety. The groundbreaking study found that Gaze-Contingent Music Reward Therapy (GC-MART) is as effective in treating social anxiety disorder as drugs from the SSRI family. The innovative treatment developed at TAU relieved the symptoms of about 50% of the study participants. The researchers hope that this therapy will soon be available as an effective alternative to psychiatric medications.
Affecting 4-12% of the Population
The study was led by Prof. Yair Bar-Haim, Director of the Adler Center for Child Development and Psychopathology, and of the Center for Traumatic Stress and Resilience at Tel Aviv University, together with research students Gal Arad and Omer Azriel from The School of Psychological Sciences at the Gershon H. Gordon Faculty of Social Sciences at Tel Aviv University Other collaborators included the NIH, the Tel Aviv Sourasky (Ichilov) and Sheba Medical Centers, and Prof. Amit Lazarov of TAU. The paper was published in the prestigious American Journal of Psychiatry.
"About 4-12% of the population will develop social anxiety disorder at some stage of their lives. Quite often, people with this disorder avoid social situations – at a heavy interpersonal, professional, and economic price." Prof. Yair Bar-Haim
Prof. Bar-Haim explains that "about 4-12% of the population will develop social anxiety disorder at some stage of their lives. Quite often, people with this disorder avoid social situations – at a heavy interpersonal, professional, and economic price. At present, psychiatry and psychology offer sufferers two types of treatment: SSRI (Selective Serotonin Reuptake Inhibitor) drugs, such as Cipralex, and CBT (Cognitive-Behavioral Therapy). CBT requires 12-20 sessions with a qualified clinical psychologist, in which symptoms are relieved through gradual exposure to the cause of anxiety. Thus, while effective, CBT is a complex treatment necessitating the presence of a highly skilled therapist and requiring patients to face their deepest fears, a requirement that often leads to treatment dropout.
"Because CBT is demanding, expensive, and not readily accessible, many patients turn to medication. However, psychiatric drugs like Cipralex have their own drawbacks: first, some patients prefer not to use psychiatric drugs; second, entire populations, such as young children, pregnant women, and individuals with specific diseases, cannot take SSRI drugs; and third, in some cases the drug has certain side effects."
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The research team (left to right): Prof. Yair Bar-Haim Gal Arad and Omer Azriel
Simple and Patient-friendly
Now, researchers from TAU have developed a third option, which is easy-to-use, quick and simple, and apparently no less effective than psychiatric drugs. Moreover, since the treatment is highly patient-friendly, a much lower dropout rate may be expected.
In the clinical trial, 105 Israeli adults with social anxiety disorder were assigned into three groups: one group was treated with SSRI drugs, in this case Cipralex; a second group was treated with GC-MART; and a control group. After ten 30-minute training sessions, about 50% of the patients provided with the new therapy demonstrated significant improvement in their symptoms - a result similar to the outcome reported for patients who took Cipralex.
"With efficacy similar to that of an existing first line drug treatment, the new treatment does not require the patient to take medications regularly. The new treatment is simple and patient friendly." Prof. Yair Bar-Haim
"The therapy we developed is based on eye-tracking combined with a musical reward," explains Prof. Bar-Haim. "The patients choose the music they would like to hear – Israeli, classical, hip hop, etc., and is shown a simulation of a crowd on a computer screen. Usually, individuals with social anxiety disorder tend to dwell on scowling or threatening facial expressions, quickly picking them out and unable to look away. Consequently, they often interpret the crowd or social situations as hostile, negative, or critical. People without social anxiety disorder, on the other hand, prefer to focus on positive or neutral faces in a crowd. In the new therapy, the music chosen by the patient provides positive feedback for a normal focus of attention on facial expressions in the crowd presented on the screen. Gradually, through training, patients’ biased attention is normalized, and symptoms recede. All participants in our trial underwent a comprehensive clinical assessment both before and after the treatment and were also asked to report on the symptoms and their severity. Results indicated that the new treatment significantly reduced symptoms of social anxiety, with an efficacy that is similar to that of SSRI drugs."
"Our findings are encouraging for both therapists and patients. With efficacy similar to that of an existing first line drug treatment, the new treatment does not require the patient to take medications regularly. The new treatment is simple and patient friendly. It does not necessitate the prolonged intervention of a highly skilled psychologist, but rather interaction with social images on a screen, and therefore potentially offers accessible, effective, and convenient treatment for social anxiety disorder," concludes Prof. Bar-Haim.
Research
Apr 16th, 2023
"Family Smoking" on The Porch
Six out of ten children whose parents restrict their smoking to the porch are at risk for being harmed by tobacco smoke
- Medicine
Many parents think that they are protecting their children by smoking on the porch or next to the window in a room. However, a new study by Tel Aviv University finds that, in contrast to such beliefs, restricting smoking to the porch does not protect most children from exposure to tobacco smoke. The research team tested for the presence of nicotine in the hair of children whose parents restrict their smoking to the porch or outside the house. Their findings are worrisome: nicotine was found in the hair of six out of ten children.
The researchers emphasize that “in Israel, home porches should be regarded as part of the environment of the home. Smoking next to a window or in another specific place in the home does not protect most children from exposure. Our recommendations are unequivocal: to reduce children’s exposure to tobacco smoke, smoking should be entirely avoided within a range of ten meters from the house. Likewise, in open areas, smokers should maintain a distance of at least ten meters from the children.”
"The Israeli situation is of great concern because in many cases, porches in Israel are directly adjacent to the living areas and may even be partially open some of the time (…) The parents mistakenly believe that the porch offers a 'safe' place to smoke." Prof. Leah (Laura) Rosen
The Porch is No 'Safe' Place
The study was led by Prof. Leah (Laura) Rosen from the School of Public Health in Sackler Faculty of Medicine, Tel Aviv University. Also participating in the study: Prof. David Zucker from the Department of Statistics and Data Science, Hebrew University, Jerusalem; Dr. Shannon Gravely from the Department of Psychology, Waterloo University, Canada; Dr. Michal Bitan from the Computer Science Department, the College of Management; Dr. Ana Rule from the Department of Health and Environmental Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore; and Dr. Vicki Meyers from the Gertner Institute for Epidemiology and Public Policy Research, Sheba Medical Center. The study was published in the International Journal of Environmental Research and Public Health.
In the first stage of the study (published about two years ago), the research team studied hair samples of the children of smoking parents for the presence of nicotine. This provides an estimate of their exposure to tobacco smoke over the past months. It was found that 70% of the children of smoking parents had measurable hair nicotine.
In the current stage of the study, the researchers examined the data by the location of parental smoking. Analysis of the data showed that in families in which the parents restricted their smoking to the porch or outdoors, 62% of the children were still exposed to tobacco smoke.
Prof. Leah (Laura) Rosen
"It is known that smoking outside the house, even when the doors and windows are fully closed, does not completely protect children from exposure to tobacco smoke," says Prof. Rosen. "The Israeli situation is of great concern because in many cases, porches in Israel are directly adjacent to the living areas and may even be partially open some of the time. The proximity allows smoke to drift from those areas to the interior of the house. The parents mistakenly believe that the porch offers a 'safe' place to smoke."
"In fact, the children are likely to be directly exposed when they come out to the porch and someone is smoking, or when smoke drifts into the house. Once in the home, the smoke is absorbed into the environment, for example, into the furniture or walls or rugs, and is then gradually discharged into the air over weeks or months."
"Further, this residual smoke, known as third hand smoke, can be absorbed into the body from the environment via swallowing or through the skin, especially among infants and small children. In addition, smoking parents transmit the toxins from the tobacco smoke on their skin, on their hands, in their hair, on their clothing. Therefore, it is recommended to brush teeth, wash hands, and change clothes after smoking, before contact with children.”
"85% of tobacco smoke is invisible, and our sense of smell is not reliable, so many parents mistakenly believe that they are protecting their children, while in fact they are exposing them to substantial health risks." Prof. Leah (Laura) Rosen
Plea to Israel's Health Ministry
Prof. Rosen notes that this new information is directly relevant to Case 1416/21 on neighbor smoking, currently being heard in the Supreme Court. The appeal against the Ministries of the Environment, Health, and Interior concerns the tobacco smoke that penetrates apartments as an environmental hazard, a claim that is supported by the definition of an environmental hazard in the Clean Air Law, the Hazard Prevention Law, and the Penal Code.
Prof. Rosen: “The results of this study show that among smoking families, restricting smoking to the porch does not protect most children from exposure to tobacco smoke. Therefore, the Health Ministry’s approach, which opposes protection for individuals from smoke incursion into their own homes to protect the smokers’ children, does not protect the children of smokers, and in addition it can cause substantial harm to neighbors and the children of neighbors. We ask the Health Ministry to reconsider its stand in light of these findings.”
"The State of Israel must make the reduction of parental smoking a national goal and invest the appropriate resources in this issue. Unfortunately, there are many misconceptions regarding when and how the exposure occurs. 85% of tobacco smoke is invisible, and our sense of smell is not reliable, so many parents mistakenly believe that they are protecting their children, while in fact they are exposing them to substantial health risks. As a society, we must safeguard citizens and distance everyone from the risks of tobacco smoke exposure, especially infants and children, pregnant women, and all vulnerable populations,” concludes Prof. Rosen.
Research
Mar 28th, 2023
Plants Emit Sounds – Especially When Stressed
In a world first, Tel Aviv University researchers record and analyze sounds distinctly emitted by plants
- Life Sciences
- Exact Sciences
- Environment
Do you talk to your plants? While you may not be able to hear them, your plants could very well be chatting away as well (perhaps they are not such great listeners after all), and that's especially true if they are having a bad day (did you forget to water them again?). For the first time in the world, TAU researchers recorded and analyzed sounds distinctly emitted by plants. The click-like sounds, resembling the popping of popcorn, are emitted at a volume similar to human speech, but at high frequencies, beyond the hearing range of the human ear. The researchers: "We found that plants usually emit sounds when they are under stress, and that each plant and each type of stress is associated with a specific identifiable sound. While imperceptible to the human ear, the sounds emitted by plants can probably be heard by various animals, such as bats, mice, and insects."
"From previous studies we know that vibrometers attached to plants record vibrations, but do these vibrations also become airborne soundwaves - sounds that can be recorded from a distance? Our study addressed this question, which researchers have been debating for many years." Prof. Lilach Hadany
Resolving Old Scientific Controversy
The study was led by Prof. Lilach Hadany from the School of Plant Sciences and Food Security at The George S. Wise Faculty of Life Sciences, together with Prof. Yossi Yovel, Head of the Sagol School of Neuroscience and faculty member at the School of Zoology and the Steinhardt Museum of Natural History, and research students Itzhak Khait and Ohad Lewin-Epstein, in collaboration with researchers from the Raymond and Beverly Sackler School of Mathematical Sciences, the Institute for Cereal Crops Research, and the Sagol School of Neuroscience – all at Tel Aviv University. The paper was published in the prestigious scientific journal Cell.
"From previous studies we know that vibrometers attached to plants record vibrations," says Prof. Hadany. "But do these vibrations also become airborne soundwaves - sounds that can be recorded from a distance? Our study addressed this question, which researchers have been debating for many years."
WATCH: Prof. Yossi Yovel and Prof. Lilach Hadany on their findings
At the first stage of the study the researchers placed plants in an acoustic box in a quiet, isolated basement with no background noise. Ultrasonic microphones recording sounds at frequencies of 20-250 kilohertz (the maximum frequency detected by a human adult is about 16 kilohertz) were set up at a distance of about 10cm from each plant. The study focused mainly on tomato and tobacco plants, but wheat, corn, cactus and henbit were also recorded.
"Our findings suggest that the world around us is full of plant sounds, and that these sounds contain information – for example about water scarcity or injury (…) We believe that humans can also utilize this information, given the right tools - such as sensors that tell growers when plants need watering." - Prof. Lilach Hadany
Mapping Plants' Complaints with AI
Before placing the plants in the acoustic box, the researchers subjected them to various treatments: some plants had not been watered for five days, in some the stem had been cut, and some were untouched. Prof. Hadany explains that their intention was to test whether the plants emit sounds, and whether these sounds are affected in any way by the plant's condition: "Our recordings indicated that the plants in our experiment emitted sounds at frequencies of 40-80 kilohertz. Unstressed plants emitted less than one sound per hour, on average, while the stressed plants – both dehydrated and injured – emitted dozens of sounds every hour."
The recordings collected in this way were analyzed by specially developed machine learning (AI) algorithms. The algorithms learned how to distinguish between different plants and different types of sounds, and were ultimately able to identify the plant and determine the type and level of stress from the recordings. Moreover, the algorithms identified and classified plant sounds even when the plants were placed in a greenhouse with a great deal of background noise.
In the greenhouse, the researchers monitored plants subjected to a process of dehydration over time and found that the quantity of sounds they emitted increased up to a certain peak, and then diminished.
"In this study we resolved a very old scientific controversy: we proved that plants do emit sounds!" says Prof. Hadany. "Our findings suggest that the world around us is full of plant sounds, and that these sounds contain information – for example about water scarcity or injury. We assume that in nature the sounds emitted by plants are detected by creatures nearby, such as bats, rodents, various insects, and possibly also other plants - that can hear the high frequencies and derive relevant information. We believe that humans can also utilize this information, given the right tools - such as sensors that tell growers when plants need watering. Apparently, an idyllic field of flowers can be a rather noisy place. It's just that we can't hear the sounds."
In future studies the researchers will continue to explore a range of intriguing questions, such as: What is the mechanism behind plant sounds? How do moths detect and react to sounds emitted by plants? Do other plants also hear these sounds? Stay tuned.
The research team
Research
Mar 27th, 2023
Tiny Robot Navigates in Physiological Environment and Captures Targeted Damaged
Meet the hybrid micro-robot: innovative technology only 10 microns across
- Medicine
- Engineering
Researchers at Tel Aviv University have developed a hybrid micro-robot, the size of a single biological cell (about 10 microns across), that can be controlled and navigated using two different mechanisms - electric and magnetic. The micro-robot is able to navigate between different cells in a biological sample, distinguish between different types of cells, identify whether they are healthy or dying, and then transport the desired cell for further study, such as genetic analysis. The micro-robot can also transfect a drug and/or gene into the captured targeted single cell. According to the researchers, the development may help promote research in the important field of 'single cell analysis', as well as find use in medical diagnosis, drug transport and screening, surgery, and environmental protection.
Inspired by Biological Micro-swimmers
The innovative technology was developed by Prof. Gilad Yossifon from the School of Mechanical Engineering and Department of Biomedical Engineering at Tel Aviv University and his team: post-doctoral researcher Dr. Yue Wu and student Sivan Yakov, in collaboration with Dr. Afu Fu, Post-doctoral researcher, from the Technion, Israel Institute of Technology. The research was published in the journal Advanced Science.
“Developing the micro-robot’s ability to move autonomously was inspired by biological micro-swimmers, such as bacteria and sperm cells. This is an innovative area of research that is developing rapidly, with a wide variety of uses in fields such as medicine and the environment, as well as a research tool.” - Prof. Gilad Yossifon
Prof. Gilad Yossifon explains that micro-robots (sometimes called micro-motors or active particles) are tiny synthetic particles the size of a biological cell, which can move from place to place and perform various actions (for example: collection of synthetic or biological cargo) autonomously or through external control by an operator. According to Prof. Yossifon, “developing the micro-robot’s ability to move autonomously was inspired by biological micro-swimmers, such as bacteria and sperm cells. This is an innovative area of research that is developing rapidly, with a wide variety of uses in fields such as medicine and the environment, as well as a research tool”.
WATCH: The Hybrid Micro-Robot
As a demonstration of the capabilities of the micro-robot the researchers used it to capture single blood and cancer cells and a single bacterium, and showed that it is able to distinguish between cells with different levels of viability, such as a healthy cell, a cell damaged by a drug, or a cell that is dying or dying in a natural 'suicide' process (such a distinction may be significant, for example, when developing anti-cancer drugs).
After identifying the desired cell, the micro-robot captured it and moved the cell to where it could be further analyzed. Another important innovation is the ability of the micro-robot to identify target cells that are not labeled - the micro-robot identifies the type of cell and its condition (such as degree of health) using a built-in sensing mechanism based on the cell's unique electrical properties.
Effective in Physiological Environments
"Our new development significantly advances the technology in two main aspects: hybrid propulsion and navigation by two different mechanisms - electric and magnetic," explains Prof. Yossifon. "In addition, the micro-robot has an improved ability to identify and capture a single cell, without the need for tagging, for local testing or retrieval and transport to an external instrument. This research was carried out on biological samples in the laboratory for in-vitro assays, but the intention is to develop in the future micro-robots that will also work inside the body - for example, as effective drug carriers that can be precisely guided to the target”.
"... the technology will support the following areas: medical diagnosis at the single cell level, introducing drugs or genes into cells, genetic editing, carrying drugs to their destination inside the body, cleaning the environment from polluting particles, drug development, and creating a 'laboratory on a particle' - a microscopic laboratory designed to carry out diagnostics in places accessible only to micro-particles." - Prof. Gilad Yossifon
The researchers explain that the hybrid propulsion mechanism of the micro-robot is of particular importance in physiological environments, such as found in liquid biopsies: "The micro-robots that have operated until now based on an electrical guiding mechanism were not effective in certain environments characterized by relatively high electrical conductivity, such as a physiological environment, where the electric drive is less effective. This is where the complementary magnetic mechanism come into play, which is very effective regardless of the electrical conductivity of the environment”.
Prof. Yossifon concludes: "In our research we developed an innovative micro-robot with important capabilities that significantly contribute to the field: hybrid propulsion and navigation through a combination of electric and magnetic fields, as well as the ability to identify, capture, and transport a single cell from place to place in a physiological environment. These capabilities are relevant for a wide variety of applications as well as for research. Among other things, the technology will support the following areas: medical diagnosis at the single cell level, introducing drugs or genes into cells, genetic editing, carrying drugs to their destination inside the body, cleaning the environment from polluting particles, drug development, and creating a 'laboratory on a particle' - a microscopic laboratory designed to carry out diagnostics in places accessible only to micro-particles.”
Research
Mar 23rd, 2023
Hyperbaric Treatment More Effective than Medicines for Fibromyalgia Caused by
Researchers say "results were dramatic" for patients who underwent hyperbaric oxygen therapy
- Medicine
Researchers from Tel Aviv University compared treatment with a dedicated protocol of hyperbaric oxygen therapy (HBOT) to the pharmacology (drugs) treatment available today for patients suffering from fibromyalgia, a chronic pain syndrome, caused by traumatic brain injury (TBI). Their findings showed that dedicated hyperbaric oxygen therapy is much more effective in reducing pain than the drug treatment and ended up healing two out of five of the participants in the study.
Chronic Pain Syndrome
The study was conducted by researchers from Tel Aviv University’s Sackler Faculty of Medicine, led by Prof. Shai Efrati, MD, from the Sagol Center for Hyperbaric Medicine and Research at the Shamir Medical Center, and Prof. Jacob Ablin, MD, from the Tel Aviv Sourasky Medical Center. The results of the study were published in the journal PLOS One.
"At the end of the treatment, two out of five patients in the hyperbaric treatment group showed such a significant improvement that they no longer met the criteria for fibromyalgia. In the drug treatment group, this did not happen to any patient." Prof. Shai Efrati
"Fibromyalgia is a chronic pain syndrome, from which between 2% - 8% of the population suffers," explains Prof. Shai Efrati. "Until 15-20 years ago, there were doctors who believed that it was a psychosomatic illness and recommended that patients with chronic pain seek mental health care. Today we know that it is a biological illness, which damages the brain's processing of the signals received from the body. When this processing is malfunctioning, you feel pain without any real damage in related locations."
"Fibromyalgia can be induced by variable triggers - from certain infections, as we have recently seen in post-COVID patients, through post-traumatic stress syndrome to head injuries. We wanted to test whether the new protocols of hyperbaric medicine can provide better results than pharmacological medicine, for patients in whom the fibromyalgia was induced by traumatic brain injury."
Prof. Shai Efrati
Dramatic Results
Hyperbaric medicine is a form of treatment in which the patients stay in special chambers where the pressure is higher than the atmospheric pressure at sea level, and where the patients breathe 100% oxygen. Hyperbaric medicine is considered safe, used in many places including Israel, and is already used to treat a long list of medical conditions.
In recent years, scientific evidence has been accumulating that certain, newly developed, dedicated hyperbaric treatment protocols can lead to the growth of new blood vessels and neurons in the brain.
"Overall, existing treatments are not good enough. [Fibromyalgia] is a chronic disease that significantly affects the quality of life, including young people, and hyperbaric medicine meets an acute need of these patients." Prof. Jacob Ablin
In their current study, the researchers from Tel Aviv University recruited 64 Israelis aged 18 and older who suffered from fibromyalgia as a result of a head injury, and randomly divided them into two groups: one group was exposed to 100% pure oxygen at a pressure of two atmospheres for 90 minutes (with fluctuations in oxygen during the treatment every 20 minutes), five days a week, for three months. The second group received the conventional pharmacological treatment (i.e., the drugs pregabalin, which is known under the trade name "Lyrica", and duloxetine, which is better known as "Cymbalta").
"The results were dramatic," says Prof. Efrati. "At the end of the treatment, two out of five patients in the hyperbaric treatment group showed such a significant improvement that they no longer met the criteria for fibromyalgia. In the drug treatment group, this did not happen to any patient. Furthermore, the average improvement in the pain threshold tests was 12 times better in the hyperbaric group compared to the medication group. And in terms of quality-of-life indicators, as reported by the patients, we saw significant improvements in all the indicators among the patients who received hyperbaric treatment."
Meets Acute Need
"Today's accepted treatment for fibromyalgia includes pharmacologic and non-pharmacologic components," says Prof. Ablin. "with respect to the pharmacologic approach, these drugs are not very effective and therefore the emphasis is on the non-pharmacological side, that is, on external correction of pain processing within the nervous system. Currently used recommendations includes aerobic activity, hydrotherapy, cognitive-behavioral therapy and movement-based therapies such as Tai Chi. In addition, quite a few patients request treatment with medical cannabis, and for some it helps."
"In the group that received hyperbaric treatment, you could see the repair of the brain tissue, while in the control group there was only an attempt to relieve the pain - without treating the damaged tissue - and of course the medication group experienced the side effects associated with drug treatment." Prof. Shai Efrati
"Overall, existing treatments are not good enough. [Fibromyalgia] is a chronic disease that significantly affects the quality of life, including young people, and hyperbaric medicine meets an acute need of these patients. Of course, these are preliminary studies, and we must follow and see what effect the medical protocol has on the patients after one, two and three years - and if it is necessary to maintain the positive results with further exposure to hyperbaric sessions."
Looking to Cure
According to Prof. Efrati, the importance of the research is in healing the damaged brain tissue - and not in treating its superficial symptoms: "In the group that received hyperbaric treatment, you could see the repair of the brain tissue, while in the control group there was only an attempt to relieve the pain - without treating the damaged tissue - and of course the medication group experienced the side effects associated with drug treatment. This is a difference in approach: to cure instead of just treating the symptoms."
"We assessed the improvement of the participants in the hyperbaric group more than a week after the last hyperbaric session. More follow-up studies are needed to see the duration of the beneficial effect of the treatment and if and for whom additional treatment will be needed. Our goal as doctors is not only to treat the symptoms but, to the extent possible, also to treat the source of the problem, thus improving the quality of life of fibromyalgia patients."
"It is important to emphasize that the dedicated hyperbaric oxygen treatment protocol found to be effective is only available in medical centers that have licensed hyperbaric chambers. Be careful of so-called 'private chambers', since these cannot provide the therapeutic protocol found to be effective, and they are not regulated or approved for medical use," cautions Prof. Efrati.
Research
Mar 20th, 2023
“Super Seaweed” Produces Natural Health Compounds and Medicine from the Sea
New Israeli technology could lead to anti-cancer, anti-diabetic, anti-inflammatory, anti-viral and antibiotic treatments
- Life Sciences
After developing an innovative technology that enables the growth of seaweed enriched with proteins and minerals such as zinc, iron, iodine, magnesium, and calcium for humans and animals, researchers from Tel Aviv University's School of Zoology at The George S. Wise Faculty of Life Sciences and the Israel Oceanographic and Limnological Research Institute (IOLR) have made a new advancement: They succeeded in significantly increasing the ability of seaweed to produce healthy natural substances, focusing on enhancing the production of bio-active compounds that offer medical benefits to humans, such as antioxidants - the concentration of which was doubled in the seaweed; natural sunscreens - its concentration tripled; and unique protective pigments of great medical value, the concentration of which increased by ten-fold.
The study was carried out with the innovative and sustainable approach of integrated aquaculture, which combines seaweed with fish cultivation, upgrading the seaweed while at the same time helping to purify the seawater and minimizing negative environmental impacts. According to the researchers, these findings may serve the pharmaceutical, cosmetics, food, and nutritional supplement industries.
Manufacturers of Valuable Compounds
The new development was led by Ph.D. student Doron Ashkenazi of Tel Aviv University and the Israel Oceanographic and Limnological Research Institute, under the guidance of Prof. Avigdor Abelson of Tel Aviv University’s School of Zoology and Prof. Alvaro Israel of the IOLR in Haifa, in collaboration with other leading researchers from Israel and around the world, including Guy Paz from IOLR; organic chemistry expert Dr. Shoshana Ben-Valid; Dr. Eitan Salomon from the National Center for Mariculture in Eilat; and Prof. Félix López Figueroa, Julia Vega, Nathalie Korbee, and Marta García-Sánchez from Malaga University in Spain. The article was published in the scientific journal Marine Drugs.
Ph.D. student Doron Ashkenazi (left) and Prof. Avigdor Abelson (right)
Doron Ashkenazi explains that “seaweed, also known as macroalgae, are marine plants that form the basis of the coastal marine ecosystem. The seaweed absorb carbon dioxide and release oxygen into the environment. They purify the water, provide food, habitat, and shelter for numerous species of fish and invertebrates. Not many know that seaweed also produce a wide variety of distinct bio-active compounds that are beneficial to humans. The seaweed living in the intertidal zone face extreme stress conditions, which include changes in salinity, temperature, desiccation [loss of moisture] conditions, changes in the availability of nutrients and high exposure to solar radiation, especially in the ultraviolet (UV) range."
"Not many know that seaweed also produce a wide variety of distinct bio-active compounds that are beneficial to humans." Doron Ashkenazi
To survive, the seaweed has developed a unique set of chemical defense mechanisms – natural chemicals that help them cope with these harsh environments. They are highly efficient natural factories that produce valuable substances that may offer significant benefits to humans.
In the current study, they sought to examine whether and how it is possible to increase and maximize the seaweed’ production of bio-active compounds, and secondary metabolites, that offer significant health benefits. These substances include antioxidants, protective pigments, and natural UV radiation filters.
A dedicated aquaculture system where the researchers grew three local species of algae
Future Looking Greener Than Ever?
To this end, the researchers developed an original and practical cultivation approach, whereby three local seaweed - Ulva, Gracilaria and Hypnea - were initially grown alongside fish effluents, and subsequently exposed to stressors including high irradiance, nutrient starvation, and high salt content.
They investigated how these changes affected the concentration of specific valuable biomaterials in the seaweed, to enhance their production. The results were impressive: antioxidant levels had doubled, seaweed natural sunscreen molecules tripled, and protective pigments were increased by ten-fold. “We developed optimal cultivation conditions and invented a new and clean way to increase the levels of healthy natural bio-active compounds in seaweed to an unprecedented level,” says Ashkenazi. “We in fact produced ‘super seaweed’ tailor designed to be utilized by the emerging health industries for food and health applications.”
“In the future, humanity will focus on creating science-based environmental solutions (...) technologies that promote recycling and the sound use of natural resources without overexploiting them.” Doron Ashkenazi
The researchers believe that in the future it will be possible to use their cultivation approach to elevate in seaweed additional natural materials with important medical properties, such as anti-cancer, anti-diabetic, anti-inflammatory, anti-viral, and ant-biotic substances.
They also emphasize that seaweed aquaculture is environmentally friendly, preserving the ecological balance, and reducing environmental risks by minimizing excessive amounts of pollutants caused by humans, reducing the emission of greenhouse gases, and lowering the carbon footprint. In this way, seaweed aquaculture can help cope with global environmental challenges such as pollution, habitat loss, and the climate crisis.
“In the future, humanity will focus on creating science-based environmental solutions, like the one we offer in this study - technologies that promote recycling and the sound use of natural resources without overexploiting them. Our study demonstrates how we can enjoy nature without harming it,” concludes Ashkenazi.
Research
Mar 14th, 2023
Do We Need 'Junk DNA'?
Researchers offer possible reason why neutral sequences in the genome of living creatures continue to exist millions of years later
- Life Sciences
A new model developed at Tel Aviv University offers a possible solution to the scientific question of why neutral sequences, sometimes referred to as "junk DNA", are not eliminated from the genome of living creatures in nature and continue to exist within it even millions of years later.
According to the researchers, the explanation is that junk DNA is often located in the vicinity of functional DNA. Deletion events around the borders between junk and functional DNA are likely to damage the functional regions and so evolution rejects them. The model contributes to the understanding of the huge variety of genome sizes observed in nature.
Border Induced Selection
The model describes a phenomenon which the team of researchers refer to as "border induced selection," and was developed under the leadership of PhD student Gil Loewenthal in the laboratory of Prof. Tal Pupko from the Shmunis School of Biomedicine and Cancer Research at the The George S. Wise Faculty of Life Sciences and in collaboration with Prof. Itay Mayrose, also from TAU's Faculty of Life Sciences. The study was published in the journal Open Biology.
Throughout evolution, the size of the genome in living creatures in nature changes. For example, some salamander species have a genome ten times larger than the human genome. "The rate of deletions and short insertions, dubbed 'indels', is usually measured by examining pseudogenes," explains Prof. Pupko. "Pseudogenes are genes that have lost their function, and in which there are frequent mutations, including deletions and insertions of DNA segments."
In previous studies that characterized the indels, it was found that the rate of deletions is greater than the rate of additions in a variety of creatures including bacteria, insects, and even mammals such as humans.
Prof. Tal Pupko
Reverse Bias for Short Segments
The question the researchers sought to answer is how the genomes are not deleted when the probability of DNA deletion events is significantly greater than DNA addition events: "We have provided a different view to the dynamics of evolution at the DNA level," says Loewenthal. "When measuring the rate of indels there will be more deletions, but the measurements are carried out in pseudogenes which are quite long sequences. We assert that in shorter neutral segments, deletions would likely remove adjacent functional segments which are essential for the functioning of the organism, and they will therefore be rejected [through 'border-induced selection']. Accordingly, we assert that when the segment is short, there will be a reverse bias – there will be more insertions than deletions - and therefore short neutral segments are usually retained."
"In our study, we simulated the dynamics of indels, while taking into account the effect of 'border-induced selection,' and compared the simulation results to the distribution of human intron lengths (introns are DNA segments in the middle of a protein-coding gene, which themselves do not code for a protein). A good match was obtained between the results of the simulations and the distribution of lengths observed in nature, and we were able to explain peculiar phenomena in the length distribution of introns, such as the large variation in intron lengths, as well as the complex shape of the distribution which does not look like a standard bell curve."
Research
Mar 13th, 2023
World's First mRNA Vaccine Against Deadly Bacteria
Israeli researchers develop vaccine that is 100% effective against bacteria lethal to humans
- Life Sciences
For the first time worldwide, a team of researchers from Tel Aviv University and the Israel Institute for Biological Research have developed an mRNA-based vaccine that is 100% effective against a type of bacteria that is lethal to humans. The study, conducted in a lab model, demonstrated that all treated models were fully protected against the bacteria. The researchers believe their new technology can enable rapid development of effective vaccines for bacterial diseases, including diseases caused by antibiotic-resistant bacteria, for example in case of a new fast-spreading pandemic.
"In our study we proved that it is, in fact, possible to develop mRNA vaccines that are 100% effective against deadly bacteria." Dr. Edo Kon
Quickly Developed
The study was led by Tel Aviv University’s Dr. Edo Kon and Prof. Dan Peer, VP for R&D and Head of the Laboratory of Precision Nano-Medicine at The Shmunis School of Biomedicine and Cancer Research at The George S. Wise Faculty of Life Sciences, in collaboration with researchers from the Israel Institute for Biological Research: Dr. Yinon Levy, Uri Elia, Dr. Emanuelle Mamroud, and Dr. Ofer Cohen. The results of the study were published in the journal Science Advances.
"So far, mRNA vaccines, such as the COVID-19 vaccines which are familiar to all of us, were assumed to be effective against viruses but not against bacteria," explains Dr. Edo Kon. "The great advantage of these vaccines, in addition to their effectiveness, is the ability to develop them very quickly: once the genetic sequence of the virus SARS-CoV2 (COVID-19) was published, it took only 63 days to begin the first clinical trial. However, until now scientists believed that mRNA vaccines against bacteria were biologically unattainable. In our study we proved that it is, in fact, possible to develop mRNA vaccines that are 100% effective against deadly bacteria."
Running RNA gel
Combining Breakthrough Strategies
The researchers explain that viruses depend on external (host) cells for their reproduction. Inserting its own mRNA molecule into a human cell, a virus uses our cells as a factory for producing viral proteins based on its own genetic material, namely replicates of itself.
In mRNA vaccines this same molecule is synthesized in a lab, then wrapped in lipid nanoparticles resembling the membrane of human cells. When the vaccine is injected into our body, the lipids stick to our cells, and consequently the cells produce viral proteins. The immune system, becoming familiar with these proteins, learns how to protect our body in the event of exposure to the real virus.
Since viruses produce their proteins inside our cells, the proteins translated from the viral genetic sequence resemble those translated from the lab-synthesized mRNA.
"If tomorrow we face some kind of bacterial pandemic, our study will provide a pathway for quickly developing safe and effective mRNA vaccines." Prof. Dan Peer
Bacteria, however, are a whole different story: They don't need our cells to produce their own proteins. And since the evolutions of humans and bacteria are quite different from one another, proteins produced in bacteria can be different from those produced in human cells, even when based on the same genetic sequence.
"Researchers have tried to synthesize bacterial proteins in human cells, but exposure to these proteins resulted in low antibodies and a general lack of protective immune effect, in our bodies," explains Dr. Kon. "This is because, even though the proteins produced in the bacteria are essentially identical to those synthesized in the lab, being based on the same 'manufacturing instructions', those produced in human cells undergo significant changes, like the addition of sugars, when secreted from the human cell."
"To address this problem, we developed methods to secrete the bacterial proteins while bypassing the classical secretion pathways, which are problematic for this application. The result was a significant immune response, with the immune system identifying the proteins in the vaccine as immunogenic bacterial proteins. To enhance the bacterial protein's stability and make sure that it does not disintegrate too quickly inside the body, we buttressed it with a section of human protein. By combining the two breakthrough strategies we obtained a full immune response."
WATCH: Prof. Dan Peer and Dr. Edo Kon on the world's first mRNA vaccine for deadly bacteria
Solution to Antibiotic-resistant Bacteria?
"There are many pathogenic bacteria for which we have no vaccines," adds Prof. Peer. "Moreover, due to excessive use of antibiotics over the last few decades, many bacteria have developed resistance to antibiotics, reducing the effectiveness of these important drugs. Consequently, antibiotic-resistant bacteria already pose a real threat to human health worldwide. Developing a new type of vaccine may provide an answer to this global problem."
"In our study, we tested our novel mRNA vaccine in animals infected with a deadly bacterium. Within a week, all unvaccinated animals died, while those vaccinated with our vaccine remained alive and well. Moreover, in one of our vaccination methods, one dose provided full protection just two weeks after it was administered. The ability to provide full protection with just one dose is crucial for protection against future outbreaks of fast-spreading bacterial pandemics. It is important to note that the COVID-19 vaccine was developed so quickly because it relied on years of research on mRNA vaccines for similar viruses. If tomorrow we face some kind of bacterial pandemic, our study will provide a pathway for quickly developing safe and effective mRNA vaccines."
The study was funded by research grants from the European Union (ERC; EXPERT) and the Shmunis Family (for Prof. Peer).
Research
Mar 2nd, 2023
New Snake Family Identified
As far as researchers are aware the Micrelapidae family includes only three species, one in Israel and neighboring countries, and two in East Africa.
- Life Sciences
An extensive international study identified a new family of snakes: Micrelapidae. According to the researchers, Micrelaps, small snakes usually with black and yellow rings, diverged from the rest of the evolutionary tree of snakes about 50 million years ago. As far as they know, the new family includes only three species, one in Israel and neighboring countries, and two in East Africa.
"Today we tend to assume that most large groups of animals, such as families, are already known to science, but sometimes we still encounter surprises, and this is what happened with Micrelapid snakes." Prof. Shai Meiri
Exploring the Micrelaps' Family Tree
The study was conducted by Prof. Shai Meiri of TAU's School of Zoology, The George S. Wise Faculty of Life Sciences, and of The Steinhardt Museum of Natural History Museum, as well as researchers from Finland, the USA, Belgium, Madagascar, Hong Kong, and Israel. The paper was published in Molecular Phylogenetics and Evolution.
"Today we tend to assume that most large groups of animals, such as families, are already known to science, but sometimes we still encounter surprises, and this is what happened with Micrelapid snakes," explains Prof Meiri.
"For years, they were considered members of the largest snake family, the Colubridae, but multiple DNA tests conducted over the last decade contradicted this classification. Since then, snake researchers around the world have tried to discover which family these snakes belong to – to no avail. In this study we joined the scientific effort."
The researchers used micro-CT technology – high-resolution magnetic imaging, to examine the snake's morphology, focusing specifically on the skull. In addition, they applied methods of deep genomic sequencing – examining about 4,500 ultra-conserved elements, namely regions in the genome that take millions of years to exhibit any change.
Prof. Meiri explains that "in addition to the DNA of Micrelaps, we sampled DNA from various snake groups to which they might have belonged. This way, we discovered some unique genomic elements in Micrelaps, which were not found in any of the other groups."
Prof. Shai Meiri
"Even through these snakes have been known for decades, they were mistakenly included in other families for many years." Prof. Shai Meiri
Family Relocation
According to the researchers their findings indicate that Micrelaps diverged from the rest of the evolutionary tree of snakes about 50 million years ago. Since then, these snakes have evolved independently, as a distinct and separate family.
Apparently, this is a very small family, including only three species: two in Kenya and Tanzania in East Africa, and one in Israel and nearby regions (northern Jordan and the Palestinian Authority, southern Syria, and southern Lebanon). The geographic dispersion suggests that these snakes probably originated in Africa, and then, at some point in their history, some of them made their way north through the Great Rift Valley.
"In this study we were able to associate a new snake family – the Micrelapidae. Even through these snakes have been known for decades, they were mistakenly included in other families for many years. Since most animals have already been classified into well-defined families, such a discovery of a new family is quite a rare occurrence in modern science," concludes Prof. Meiri.
Research
Feb 26th, 2023
Researchers Discover Mechanism that Facilitates Formation of Brain Metastases
Findings could help predict metastatic recurrence in the brain and a worse prognosis
- Medicine
Brain metastases are one of the deadliest forms of cancer metastasis, with grave survival rates of less than one year in many cases. The incidence of brain metastases has been increasing in recent years and developing better therapeutic strategies for brain metastasis is an urgent need. In a new study from Tel Aviv University, researchers identified and characterized a new mechanism that facilitates the formation of brain metastases and found that impairing this mechanism significantly reduced the development of brain metastases in lab models.
"The findings establish LCN2 as a new prognostic marker and a potential therapeutic target." Prof. Neta Erez
On the Radar: LCN2
The research was led by Prof. Neta Erez, head of the laboratory for the biology of tumors from the Department of Pathology at the Sackler Faculty of Medicine, and members of her team: Omer Adler, Yael Zeit, and Noam Cohen, in collaboration with Prof. Shlomit Yust Katz from Rabin Medical Center (Beilinson Hospital) and Prof. Tobias Pukrop from Regensburg Hospital, Germany. The study was supported by the Melanoma Research Alliance (MRA), the Cancer Biology Research Center at Tel Aviv University, the Personalized Medicine Program of the Israel Science Foundation (ISF IPMP) and the German Cancer Research Foundation (DFG), and was published in the journal Nature Cancer.
In this new study, the researchers show that Lipocalin-2 (LCN2) [a protein which in humans is encoded by the LCN2 gene] is a key factor in inducing neuroinflammation in the brain. Moreover, the researchers found that high LCN2 levels in patients’ blood and brain metastases from several types of cancer are associated with disease progression and reduced survival.
LCN2 is a secreted protein that functions in the innate immune system and was originally discovered due to its ability to bind iron molecules and as part of the inflammatory process in fighting bacterial infection. LCN2 is produced by a large variety of cells and was shown to be involved in multiple cancer-related processes.
"Our findings reveal a previously unknown mechanism, mediated by LCN2, which reveals a central role for the mutual interactions between immune cells recruited to the brain (granulocytes) and brain glial cells (astrocytes) in promoting inflammation and in the formation of brain metastases. The findings establish LCN2 as a new prognostic marker and a potential therapeutic target," says Prof. Neta Erez.
"In blood and tissue samples from patients with brain metastases from three types of cancer, blood LCN2 levels were correlated with disease progression and with shorter survival, which positions LCN2 as a potential prognostic marker for brain metastases." Prof. Neta Erez
LCN2 as a Predictive Marker for Brain Metastases
The researchers used models of melanoma and breast cancer brain metastases to reveal the mechanism by which neuroinflammation is activated in the metastatic niche in the brain.
"We show that signals secreted into the blood from the primary tumor stimulate pro-inflammatory activation of astrocytes in the brain. The astrocytes promote the recruitment of inflammatory cells from the bone marrow (granulocytes) into the brain, and they in turn become a main source of signaling by LCN2," explains Prof. Erez.
"We demonstrated the importance of LCN2 for the development of metastases by genetically inhibiting its expression in mice, which resulted in a significant decrease in neuroinflammation and reduced brain metastases. Moreover, in blood and tissue samples from patients with brain metastases from three types of cancer, blood LCN2 levels were correlated with disease progression and with shorter survival, which positions LCN2 as a potential prognostic marker for brain metastases."
Prof. Erez adds: "We analyzed the LCN2 protein levels in the blood and cerebrospinal fluid (CSF) of mice with brain metastases and found that LCN2 levels increased greatly in mice with melanoma and breast cancer metastases compared to healthy mice. Importantly - an increase in blood LCN2 preceded the detection of brain metastases by MRI. Furthermore, the mice in which LCN2 levels were very high developed brain metastases later, further establishing LCN2 as a predictive marker for brain metastases.”
The researchers also examined whether LCN2 is elevated in the blood of melanoma patients at the time of initial diagnosis, and whether it can be a prognostic factor. The findings indicated that patients with melanoma had significantly higher levels of LCN2 in their blood compared to samples from healthy individuals. Strikingly, patients who developed brain metastases displayed significantly higher levels of LCN2 even before the diagnosis of the metastases, and high levels of LCN2 in the blood correlated with worse survival.
"We have identified a new mechanism in which LCN2 mediates the communication between immune cells from the bone marrow and supporting cells in the brain, activates inflammatory mechanisms and thus helps the progression of metastatic disease in the brain, and demonstrated its importance. The functional and prognostic aspects of LCN2 that we have identified in brain metastases in mouse models as well as in cancer patients suggest that targeting LCN2 may be an effective therapeutic strategy to delay or prevent the recurrence of brain metastases," summarizes Prof. Erez.
Research
Feb 14th, 2023
Does a Food Sharing Economy Benefit the Environment?
According to researchers it depends on how the saved money is spent
- Exact Sciences
- Environment
Researchers from Tel Aviv University and Ben Gurion University explored the true benefit of the so-called "digital food sharing economy": when people advertise and pass on surplus food items to others instead of throwing them away. Is this indeed an environmentally friendly practice that saves resources and significantly reduces harm to the environment? The researchers focused on the effectiveness of food sharing according to three environmental indicators: water depletion, land use, and global warming. They found that a significant proportion of the benefit to the environment is offset when the money saved is then used for purposes that have a negative environmental impact.
"While there is nothing new about sharing food, digitalization has lowered transaction costs substantially, allowing food to be shared not only within social circles of family and friends but also with absolute strangers." Dr. Tamar Makov
Sharing Food Got Cheaper
The study was led by Tamar Meshulam, under the guidance of Dr. Vered Blass of the Porter School of Environment and Earth Sciences at the Raymond & Beverly Sackler Faculty of Exact Sciences of Tel Aviv University and Dr. Tamar Makov of Ben-Gurion University, and in collaboration with Dr. David Font-Vivanco, an expert on “rebound effect.” The article won the award for the “Best Article” at the PLATE (Product Lifetimes and the Environment) conference and was published in the Journal of Industrial Ecology.
“Food waste is a critical environmental problem," explains Tamar Meshulam: "We all throw away food, from the farmer in the field to the consumer at home. In total, about a third of the food produced in the world is lost or wasted. This wasted food is responsible for roughly 10% of GHG [greenhouse gas] emissions, and the land area used to grow food that is then wasted is equal in size to the vast territory of Canada! That’s why it is so important to look for ways to reduce food waste and examine their potential contribution to mitigating climate change.”
According to Dr. Tamar Makov, “Internet platforms for sharing food are gaining popularity all over the world and are seen as a natural solution that can help tackle both food waste and food insecurity at the same time. While there is nothing new about sharing food, digitalization has lowered transaction costs substantially, allowing food to be shared not only within social circles of family and friends but also with absolute strangers."
“Is it possible that at least some of the money saved is then spent on carbon intensive products and services that negate the benefit of sharing? (…) In this study, we sought to examine this troubling issue in depth." Dr. Vered Blass
From left to right: Dr. Vered Blass (Tel Aviv University) and Dr. Tamar Makov (Ben-Gurion University)
Where Does the Money Go?
"At the same time, sharing platforms as well as other digitally enabled food waste reduction platforms (e.g., too good to go) can save users a lot of money, which raises the question of what do people typically do with such savings? Considering what people do with the money they save via sharing platforms is critical for evaluating environmental impacts,” notes Makov.
Dr. Vered Blass adds: “Is it possible that at least some of the money saved is then spent on carbon intensive products and services that negate the benefit of sharing?" She offers an example to illustrate: "Let’s say that for one month a young couple lives only on food they obtained for free through a sharing platform, and then they decide to use the money they saved to fly abroad. In such a case, it’s obvious that the plane they will be flying in creates pollution that harms the environment more than all the benefits of sharing. In this study, we sought to examine this troubling issue in depth.”
"As long as our savings are measured in money, and the money is used for additional expenses, the rebound effect will erode our ability to reduce environmental burdens through greater efficiency." The research team
“Rebound Effect” Detected
The researchers chose to focus on the app OLIO, an international peer-to-peer food-sharing platform, and specifically on its activity in the United Kingdom between the years 2017 and 2019.
Combining models from the fields of industrial ecology, economics, and data science, they measured the benefits of sharing food using three environmental indicators: global warming, the depletion of water sources, and land use. To understand how OLIO users spend their savings they used statistical data published by the UK Office for National Statistics on household spending by consumption purpose to as COICOP (classification of individual consumption according to purpose).
“The location in which the food-sharing took place allowed us to assign each collecting user to their UK income percentile," shares Meshulam. "We found that about 60% of the app's users belong to the bottom five deciles, while about 40% of the shares were carried out by the top five deciles. We also found that the second and tenth deciles made up a relatively large number of shares, so we chose to focus on them, along with data on the general population – what they spend their money on, and what the significance of these consumption habits is regarding the savings made possible by sharing.”
The researchers performed a variety of statistical analyses, which yielded fascinating findings. In many cases, there was a considerable gap, or “rebound effect” between the expected environmental benefit and the benefit that was attained.
This rebound effect changed depending on the population and the environmental impact category. Tamar Meshulam cites several examples: For the general population, 68% of the benefit was offset in the global warming category, about 35% was offset in the water depletion category, and about 40% was offset in the land use category. Furthermore, in households that used half of their savings on food, the rebound effect in all categories increased to 80-95%.
The researchers sum up: “The conclusion from our research is that the actual environmental benefits from efficiency improvements often fall short of expectations. This is because the infrastructures supporting human activities are still carbon intensive. As long as our savings are measured in money, and the money is used for additional expenses, the rebound effect will erode our ability to reduce environmental burdens through greater efficiency.”
The researchers also examined what the results would have been if the sharing had been conducted in 2011 (these results are not included in this article). A comparison with the findings of 2019 shows a significant improvement. The explanation for this is that in recent years, Britain has made great efforts to switch to renewable energies, and the impact of this is evident in the decrease of greenhouse gas emissions. The bottom line? The researchers conclude that "as our findings demonstrate, we need to combine a transition to green infrastructure with green consumerism. Each of these individually will not achieve the desired and critical impact needed for humanity and the planet.”
