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Doctor on laptop next to image of computer brain

Research

Jan 23rd, 2023
Researchers Uncover New Factors Linked to Williams Syndrome

Findings may contribute to development of treatments to enable normal expression of genes essential for brain development in people suffering from the syndrome

  • Social Sciences

Williams syndrome is a relatively rare, multisystem genetic syndrome that causes disorders in brain development. A new study by the Tel Aviv University and Hebrew University found that abnormal processes lead to disruption in the expression of genes essential for brain development in people suffering from the syndrome. The researchers believe their findings may contribute to the future development of targeted treatments that will enable normal expression of the affected genes identified in the research.

 

Looking Beyond Chromosome 7

The research was led by Dr. Boaz Barak from the School of Psychological Sciences and the Sagol School of Neuroscience at Tel Aviv University and Dr. Asaf Marco from the Faculty of Agriculture, Food and Environment of the Hebrew University. Also participating in the research were Dr. Sari Trangle, Mr. Gilad Levy and Ms. Ela Bar from Dr. Barak's laboratory, and Dr. Tali Rosenberg and Ms. Hadar Parnas from Dr. Marco's laboratory. The research findings were published in the prestigious journal Molecular Psychiatry from the Nature publishing group.

 

 

"We wanted to examine whether the Williams Syndrome is also characterized by defects in the genomes contained in brain cells which prevent the proper expression of essential genes." Dr. Boaz Barak

 

 

Dr. Barak: “Williams syndrome is a rare, multisystem genetic syndrome that includes disorders in brain development that lead to heightened social interactions, mental retardation, and other characteristic features. Past research has revealed that twenty-five genes are missing from the DNA on chromosome number seven of people with Williams syndrome, and the study of the syndrome to date has mainly focused on those missing genes and their functions."

 

"We wanted to examine whether the syndrome is also characterized by defects in the genomes contained in brain cells which prevent the proper expression of essential genes. Specifically, we asked: ‘Is it possible that certain genes are not expressed properly in the brains of people with Williams syndrome due to the phenomenon of methylation - when a molecule known as a 'methyl group' is located on a certain gene that is present in the genome, preventing it from expressing itself properly?".

 

To illustrate the phenomenon of the missing genes, Dr. Barak took an instruction book in which some of the pages were torn out. As a result of the missing pages, anyone following the instructions would make mistakes. Similarly, hiding some of the letters in the pages left in the book with a black marker would result in instructions being corrupted, just like methylation on an existing gene disrupts its expression.

 

Methylation is in many cases a normal mechanism in the cells of the body, as its role is to prevent expression of certain genes when appropriate. However, when there are disruptions in the correct application of methylation, the abnormal expression of the genes may lead to impairments in cell function, and subsequently cause damage to various organs, including to normal brain development.

 

Dr. Boaz Barak  from the School of Psychological Sciences and the Sagol School of Neuroscience at Tel Aviv University

 

Uncovering New Factors

The researchers examined human brain tissues taken from adults with and without Williams syndrome who died of causes unrelated to the syndrome and donated their brains to science.

 

“We focused on samples from the frontal lobe, the area of the brain that is responsible for brain functions such as cognition and decision-making," Dr. Barak explained. "In a previous study, we located in this area damage to the characteristics of the nerve cells and the cells that support nerve cell activity in people with Williams syndrome. In this study, we examined all the genes in all the cells of the frontal lobe to determine whether there are genes in people with Williams syndrome that have undergone abnormal methylation processes, i.e., increased or decreased gene silencing compared to a brain with typical development.”

 

 

"We uncovered significant information about the defective expression of genes in people with Williams syndrome. While these genes are fully present in the genome of the brain cells, until now it was not known that these abnormally regulated genes are involved in the syndrome." Dr. Asaf Marco.

 

 

The researchers found that indeed in people with Williams syndrome abnormal methylation does exist in this area of the brain, resulting in disruption of the normal expression of many genes related to the normal development of the brain's neural functions, such as regulation of social behavior (people with Williams syndrome are known to be overly friendly), cognition, plasticity of the brain, and cell survival.

 

“We uncovered significant information about the defective expression of genes in people with Williams syndrome. While these genes are fully present in the genome of the brain cells, until now it was not known that these abnormally regulated genes are involved in the syndrome," says Dr. Marco.

 

 

"Building on our findings, it will be possible to focus future efforts on the development of targeted treatments that will reach the disrupted sites that we identified in the study in order to 'correct' the defective expressions." Dr. Boaz Barak

 

 

Next Step: Target Disrupted Sites

"In addition, one of our main findings is that the disruptions in methylation do not have to appear near the gene whose function is impaired, and sometimes the disruptions are located far away from it. This information is critical because it allows us to better understand the spatial organization of DNA and its effect on gene control."

 

He adds that, "since we know of enzymes that are able to remove or add methyl molecules, the next challenge will be to precisely direct those enzymes to the disrupted sites identified in our research, with the aim of allowing the genes to be properly expressed.”

 

Dr. Barak concludes: "Our research revealed new factors related to the disabilities that characterize Williams syndrome. Instead of focusing on the effects of the missing gene, as has been done until now, we shed light on many more genes that are expressed in a defective manner. Building on our findings, it will be possible to focus future efforts on the development of targeted treatments that will reach the disrupted sites that we identified in the study in order to 'correct' the defective expressions.”

robot holding up flower for another robot to smell

Research

Jan 22nd, 2023
Robot, Can You Smell This?

In a scientific first, a robot can “smell” using a biological sensor

  • Life Sciences
  • Engineering

After having developed a robot that hears through the ear of a locust, researchers from Tel Aviv University have succeeded in equipping a robot with the sense of smell, using a biological sensor. The sensor sends electrical signals as a response to the presence of a nearby odor, which the robot can detect and interpret. The researchers successfully connected the biological sensor to an electronic system and using a machine learning algorithm, were able to identify odors with a level of sensitivity 10,000 times higher than that of a commonly used electronic device. The researchers say "The sky's the limit," and believe that this technology may also be used in the future to identify explosives, drugs, diseases, and more.

 

WATCH: The first robot with a biological nose. Only at Tel Aviv University.

 

 

 

“Man-made technologies still can’t compete with millions of years of evolution. One area in which we particularly lag behind the animal world is that of smell perception (…) When they want to check if a passenger is smuggling drugs [at the airport], they bring in a dog to sniff him." Dr. Ben Maoz and Prof. Amir Ayali

 

 

Technology Lags Behind Evolution

The biological and technological breakthrough was led by doctoral student Neta Shvil of Tel Aviv University’s Sagol School of Neuroscience, Dr. Ben Maoz of the Fleischman Faculty of Engineering and the Sagol School of Neuroscience, and Prof. Yossi Yovel and Prof. Amir Ayali of the School of Zoology and the Sagol School of Neuroscience. The results of the study were published in the prestigious journal Biosensor and Bioelectronics.

 

Dr. Maoz and Prof. Ayali explain: “Man-made technologies still can’t compete with millions of years of evolution. One area in which we particularly lag behind the animal world is that of smell perception (…) When they want to check if a passenger is smuggling drugs [at the airport], they bring in a dog to sniff him."

 

"In the animal world, insects excel at receiving and processing sensory signals. A mosquito, for example, can detect a 0.01 percent difference in the level of carbon dioxide in the air. Today, we are far from producing sensors whose capabilities come close to those of insects.”

 

The researchers point out that, in general, our sensory organs, such as the eye, ear and nose – as well as those of all other animals – use receptors that identify and distinguish between different signals. Then, the sensory organ translates these findings into electrical signals, which the brain decodes as information. The challenge of biosensors is in the connection of a sensory organ, like the nose, to an electronic system that knows how to decode the electrical signals received from the receptors.

 

Dr. Ben Maoz and doctoral student Neta Shvil

 

 

“Nature is much more advanced than we are, so we should take advantage of that." Dr. Ben Maoz. 

 

 

10,000 Times More Sensitive to Smell

“We connected the biological sensor [to the electronic system] and let it smell different odors while we measured the electrical activity that each odor induced," explains Prof. Yovel. "The system allowed us to detect each odor at the level of the insect’s primary sensory organ."

 

"Then, in the second step, we used machine learning to create a ‘library’ of smells. In the study, we were able to characterize 8 odors, such as geranium, lemon and marzipan, in a way that allowed us to know when the smell of lemon or marzipan was presented. In fact, after the experiment was over, we continued to identify additional different and unusual smells, such as various types of Scotch whiskey. A comparison with standard measuring devices showed that the sensitivity of the insect’s nose in our system is about 10,000 times higher than the devices that are in use today.”

 

“Nature is much more advanced than we are, so we should take advantage of that," says Dr. Maoz. "The principle we have demonstrated can be used and applied to other senses, such as sight and touch. For example, some animals have amazing abilities to detect explosives or drugs; the creation of a robot with a biological nose could help us preserve human life and identify criminals in a way that is not possible today. Some animals can detect diseases. Others sense earthquakes. The sky is the limit.”

 

What's next? The researchers plan to give the robot a navigation ability to allow it to localize the odor source and later, its identity. 

 

Will he be able to retire soon? A working dog searches for hazardous materials at the airport

Medical Clown and girl nose to nose (Photo: The Dream Doctors Project, Medical Clowning in Action)

Research

Jan 17th, 2023
Medical Clowns - No Laughing Matter

Israeli researchers find that medical clowns contribute significantly to the achievement of medical therapeutic goals

  • Medicine

You see them stroll around in the hospitals' toughest wards with their red noses, colorful clothes, and unwavering smiles, spreading laughter and cheerfulness wherever they go. They are the medical clowns: trained professionals whose goal is to change the hospital environment through humor. 

 

A new study tested and categorized the skills of medical clowns and found that their importance goes far beyond contributing to a patient's good mood. The researchers identified 40 different skills of medical clowns, including establishing an emotional connection and creating a personal relationship with the patient, expressing the patient's frustrations and difficulties to the medical staff, increasing the patient’s motivation to adhere to medical treatment, distracting the patient from pain, and creating a joyful atmosphere.

 

Medical clowns working alongside other therapists (Photo: The Dream Doctors Project, Medical Clowning in Action)

 

Not Just for Entertainment Purposes

The research was conducted under the leadership of Prof. Orit Karnieli-Miller, with Dr. Lior Rosenthal, both from the Department of Medical Education at TAU's Sackler Faculty of Medicine, in collaboration with Ms. Orna Divon-Ophir, Dr. Doron Sagi, Prof. Amitai Ziv and Ms. Liat Pessach-Gelblum from the Israel Center for Medical Simulation (MSR). The study was published in Qualitative Health Research, a leading journal in the field of health.

 

The researchers show that not only do medical clowns help the patients and their family members, but also the medical team and the achievement of treatment goals.

 

Through use of different communication skills, clowns make it easier for the patient to cooperate with various treatments. The medical clowns work in a team with other therapists, know how to intervene and help whenever an argument or crisis should arise to advance treatment.

 

 

"From the moment they enter the room, the clowns form a bond with the patients, strengthen them, and give them power and status within the medical system." Prof. Orit Karnieli-Miller. 

 

 

Decoding their "Secret Magic"

Studies conducted throughout the years have shown the clowns’ positive influence on the hospital environment through humor, as well as helping patients deal with pain. However, no studies have empirically mapped the skills they use and their therapeutic goals to help understand their “secret magic.” In addition, there was a lack of broad understanding of how clowns can help children, teenagers, and their parents in various challenging situations of distress and difficulty, as well as how they can help patients and medical teams achieve treatment goals. This lack of appreciation of the potential benefits of utilizing the services of medical clowns meant that patients and medical teams would occasionally be reluctant to cooperate with them.

 

As part of the new study, the researchers focused on qualitative, in-depth systematic identification of the skills of medical clowns through observation and analysis of their actions in challenging encounters with adolescents, parents, and medical staff.

 

Medical clowns help patients and medical teams achieve treatment goals (Photo: The Dream Doctors Project, Medical Clowning in Action)

 

The team analyzed videotaped sessions of medical clowns in various simulated situations and conducted in-depth interviews with expert medical clowns. The researchers identified 40 different skills used by the medical clowns to achieve four therapeutic goals:

 

1) building a relationship and connecting to the needs and desires of the patients

2) dealing with emotions and difficulties

3) increasing the patient’s motivation to adhere to the treatment plan

4) increasing the patient’s sense of control and providing encouragement to patients

 

The clowns examined in the study were trained and recruited by the "Dream Doctors Project”, a non-profit association that employs medical clowns as part of the paramedical system in Israeli hospitals, and trains them to work within multi-disciplinary teams. The Tel Aviv University researchers collaborated with the Israel Center for Medical Simulation (MSR), which created a simulation-based workshop focused on developing the skills of experienced medical clowns.

 

"From the moment they enter the room, the clowns form a bond with the patients, strengthen them, and give them power and status within the medical system," explains Prof. Karnieli-Miller. "They do this through an initial connection to the patients’ voice, and even to the patients’ reluctance to implement therapeutic recommendations - an emotional connection that often results in the patient changing their position and cooperating with the medical staff."

 

Providing the patient with an increased sense of control and courage to face their challenges (Photo: The Dream Doctors Project, Medical Clowning in Action)

 

According to Prof. Karnieli-Miller the medical system is hierarchical, and it is not always easy for patients to navigate. Therefore, one of the skills of medical clowns is to place themselves in the lowest position in the medical setting. By doing so, they empower the patients by giving them a sense of power and control, including the choice of whether to allow the clown to enter the room as well as to dictate the nature of the patient’s role vis-à-vis that of the clown. This provides the patient with an increased sense of control and courage to face their challenges.

 

The researchers emphasize that the clowns are very aware of the emotional difficulty associated with staying in a hospital and dealing with an illness. To help deal with these issues, the clowns sometimes distract the patient by using props, humor, and imagination. Other skills include allowing the patient to direct their frustrations towards them, away from medical staff or parents.

 

Depending on the situation the clowns may also use a comforting touch, soothing music, empathetic listening, or a reinforcing statement to provide an environment where the patient feels comfortable to express their feelings. A patient’s ability to gain legitimacy is important and is strengthened by the clowns.

 

Prof. Orit Karnieli-Miller

 

 

"Mapping the skills and goals of the medical clowns improves their understanding of their role and may help other health professionals appreciate their work methods and the benefits of incorporating these methods into their own practices when faced with similar challenges" Prof. Orit Karnieli-Miller.

 

Learning from Medical Clowns' Methods

"Mapping the skills and goals of the medical clowns improves their understanding of their role and may help other health professionals appreciate their work methods and the benefits of incorporating these methods into their own practices when faced with similar challenges,” adds Prof. Karnieli-Miller.

 

"This research is important because it allows the clowns to enhance their training program and refine their diverse skills to achieve the various therapeutic goals appropriate for different patients, as well as helping health professionals collaborate with the medical clowns. If professionals in the healthcare field gain a clear understanding of how and when to cooperate with the medical clowns, they will be able to help patients overcome challenges, and at the same time they may be more tolerant of the clowns' ‘disruption’ of the hospital care regimen. This appreciation of the clowns’ contribution will provide the clowns with the time and space to connect with patients and help and encourage patients to become more active participants in their treatment plan,” she concludes.

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