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."
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
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).
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
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.
Findings could help predict metastatic recurrence in the brain and a worse prognosis
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.
According to researchers it depends on how the saved money is spent
- Exact Sciences
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.”
New study shows that artificial light at night can be harmful to ecosystems, biodiversity, and human health
- Life Sciences
A new study from Tel Aviv University's School of Zoology tested the impact of prolonged low-intensity light pollution on two species of desert rodents: the diurnal golden spiny mouse, and the nocturnal common spiny mouse. The findings were highly disturbing: on two different occasions, entire colonies exposed to ALAN (Artificial Light At Night) died within days, and reproduction also decreased significantly compared to control groups. According to the researchers, the results show clearly for the first time that light pollution can be extremely harmful to these species, and suggest they may be harmful to ecosystems, biodiversity, and even human health.
"According to latest studies, about 80% of the world's human population is exposed to ALAN, and the area affected by light pollution grows annually by 2-6%. In a small and overcrowded state like Israel, very few places remain free of light pollution." Hagar Vardi-Naim
Humans Changed the Rules
The study was led by Prof. Noga Kronfeld-Schor, Chief Scientist of Israel's Ministry of Environmental Protection, and PhD student Hagar Vardi-Naim, both from TAU's School of Zoology and the Steinhardt Museum of Natural History. The paper was published in Scientific Reports.
"We have been studying these closely related rodent species for years. They both live in Israel's rocky deserts: the golden spiny mouse (Acomys russatus) is diurnal [active during the day], and the common spiny mouse (A. cahirinus) in nocturnal [active during the night]," explains Prof. Kronfeld-Schor. "The two species share the same natural habitat but use it at different times to avoid competition. By comparing closely related species that differ in activity times, we gain new insights into the biological clock and its importance to the health of both animals and humans."
Hagar Vardi-Naim notes that, "in most species studied to date, including humans, the biological clock is synchronized by light. This mechanism evolved over millions of years in response to the daily and annual cycles of sunlight – day and night and their varying lengths that correspond to the change of seasons. Different species developed activity patterns that correspond to these changes in light intensity and daylength and developed anatomical, physiological and behavioral adaptations suitable for day or night activity and seasonality."
"However, over the last decades, humans have changed the rules by inventing and extensively using artificial light, which generates light pollution. According to latest studies, about 80% of the world's human population is exposed to ALAN, and the area affected by light pollution grows annually by 2-6%. In a small and overcrowded state like Israel, very few places remain free of light pollution. In our study, we closely monitored the long-term effects of ALAN on individuals and populations under semi-natural conditions."
"We had seen no preliminary signs (…) We assume that exposure to ALAN had impaired the animals' immune response, leaving them with no protection against some unidentified pathogen [organism causing disease to its host]." Prof. Noga Kronfeld-Schor
Prof. Noga Kronfeld-Schor
Dramatic Turn of Events
In the study, the researchers placed 96 spiny mice, males and females in equal numbers, in eight spacious outdoor enclosures at TAU's Zoological Research Garden. The enclosures simulated living conditions in the wild: all animals were exposed to natural environmental conditions, including the natural light/dark cycle, ambient temperatures, humidity, and precipitation. Each enclosure contained shelters, nesting materials and access to sufficient amounts of food. The experimental enclosures were exposed to low-intensity ALAN (like a streetlamp in urban areas) of different wavelengths (colors) for 10 months: two enclosures were exposed to cold white light, two to warm white (yellowish) light, and two to blue light, while two of the enclosures remained dark at night and served as controls. All animals were marked to enable accurate monitoring of changes in behavior and physical condition. The experiment was conducted twice in two successive years.
"The average life expectancy of spiny mice is 4-5 years, and our original plan was to monitor the effects of ALAN on the same colonies, measuring the effects on reproductive output, wellbeing and longevity," says Prof. Kronfeld-Schor. "But the dramatic results thwarted our plans: on two unrelated occasions, in two different enclosures exposed to white light, all animals died within several days. We had seen no preliminary signs, and autopsies at TAU's Faculty of Medicine and the Kimron Veterinary Institute in Beit Dagan revealed no abnormal findings in the dead spiny mice. We assume that exposure to ALAN had impaired the animals' immune response, leaving them with no protection against some unidentified pathogen. No abnormal mortality was recorded in any of the other enclosures, and as far as we are aware, no similar event has ever been documented by researchers before."
"Our findings show that light pollution, especially cold white and blue light, increases mortality and disrupts reproduction, and thus may be detrimental to the fitness and survival of species in the wild. This adverse effect can have far-reaching consequences at the current wide distribution of light pollution." Prof. Noga Kronfeld-Schor
Other findings also indicated that exposure to ALAN disrupts the reproductive success of spiny mice: "In the wild both species of spiny mice breed mainly during summer, when temperatures are high, and the newborn pups are most likely to survive," shares Hagar Vardi-Naim. "Artificial light, however, seemed to confuse the animals. The common spiny mice began to breed year-round but produced a lower number of pups per year. Pups born during winter are not expected to survive in nature, which would further reduce the species' reproductive success in the wild."
"The reproduction of golden spiny mice was affected in a different way: colonies exposed to ALAN continued to breed in the summer, but the number of young was reduced by half compared to the control group, which continued to thrive and breed normally. These findings are in accordance with the fact that in seasonal long day breeders the cue for reproduction is day length."
Additional tests revealed that exposure to ALAN caused physiological and hormonal changes – most significantly in the level of cortisol, an important stress hormone involved in the regulation and operation of many physiological pathways, including the regulation of the immune system. Lab tests indicated that exposure to blue light increased cortisol levels of golden spiny mice, while white light reduced cortisol levels of golden spiny mice males in winter.
"Our findings show that light pollution, especially cold white and blue light, increases mortality and disrupts reproduction, and thus may be detrimental to the fitness and survival of species in the wild. This adverse effect can have far-reaching consequences at the current wide distribution of light pollution. Our clear results are an important step toward understanding the impact of light pollution on biodiversity and will help us promote science-based policies, specifically with regard to the use of artificial light in both built and open areas. In future studies we plan to investigate what caused the extensive deaths in the enclosures exposed to ALAN, focusing on the effect of light pollution exposure on the immune system," concludes Prof. Kronfeld Schor.
Age-related Macular Degeneration (AMD) is a leading cause for loss of eyesight at an advanced age
Researchers at Tel Aviv University identified a new genetic risk factor for the complex eye disease AMD (Age-related Macular Degeneration), a leading cause for loss of eyesight at an advanced age. For the first time, the researchers identified proteins that play a key role in the development and functioning of the tissue affected by the disease, found their exact sites in the genome, and discovered the connection between variations in these genomic regions and the risk for AMD. The researchers: "The new discovery enhances our understanding of the previously unknown function of genomic regions outside the genes. The method we applied may enable the deciphering of additional genetic mechanisms involved in various complex genetic diseases."
"Comparative studies have identified whole genomic regions that are probably related to the disease but were unable to pinpoint any specific feature in these regions and define it as a risk factor. Our study addressed this problem." Prof. Ran Elkon
Decoding Mechanisms of a Complex Disease
The study was led by Prof. Ruth Ashery-Padan and Prof. Ran Elkon and their research teams, Mazal Cohen Gulkar, Naama Mesika, Ahuvit David, and May Eshel, from the Department of Human Molecular Genetics and Biochemistry at the Sackler Faculty of Medicine and the Sagol School of Neuroscience at Tel Aviv University. The paper was published in PLOS Biology.
Prof. Ashery-Padan explains that "one of the greater challenges in genetic research today is decoding the genetic mechanisms of complex diseases caused by a combination of several different genetic and environmental factors (rather than an identifiable defect in a single gene). Diabetes, bowel diseases, and various mental illnesses are just a few examples. In our study we chose to focus on AMD, which causes degeneration of the central retina - a major cause of loss of vision at an advanced age in developed countries."
Prof. Elkon adds: "AMD has a significant genetic component. Studies comparing the genomes of people with and without AMD (as well as a range of other complex genetic diseases) have found differences in several genomic regions, probably associated with risk factors for the disease. However, these differences were not detected in any specific gene, but rather in the extensive regions that stretch between the genes, whose functions and modes of operation are still largely unknown. In fact, comparative studies have identified whole genomic regions that are probably related to the disease but were unable to pinpoint any specific feature in these regions and define it as a risk factor. Our study addressed this problem."
The study focused on the cells of a layer of tissue called retinal pigmented epithelium (RPE), which supports photoreceptors in the retina, and is essential for their initial development as well as their survival throughout an individual's lifetime. According to the researchers, this tissue is affected right from the earliest stages of AMD.
Prof. Ruth Ashery-Padan
"Our findings provide new insight into a previously unsolved issue: the functions and mode of operation of genomic sequences located outside the genes, and how they are involved in complex genetic diseases." Prof. Ruth Ashery-Padan
Novel Research Methodology
"First, we wanted to understand the genetic mechanism that activates and regulates the specific activity of pigmented epithelium cells," says Prof. Ashery-Padan. "Through a series of experiments, knocking down different proteins in both a mouse model and human cells, we identified two key proteins, LHX2 and OTX2, which together dictate the expression of many genes unique to this tissue. The proteins act as transcriptional activators - binding to specific regulatory sites in the genome to determine which genes will be expressed in a particular cell."
The next challenge was mapping the precise locations of the two proteins in the genome. The researchers used the innovative technology ChIP-seq – a DNA sequencing method that identifies binding sites where proteins bind to the DNA.
"We found that the binding sites of the two proteins were quite close to each other," explains Prof. Elkon. "Moreover, these same sites had previously been identified as related to risk factors for AMD (namely, sequences that showed differences between people with and without AMD). We assume that due to changes in DNA sequences in these genomic regions, transcriptional proteins cannot easily find and bind with their binding sites. This reduces the expression of the nearby gene regulated by the transcriptional proteins, which encodes an ion channel known as important to eye function. The decrease in the gene's activity affects the entire tissue, increasing the risk for development of AMD."
Prof. Ashery-Padan sums up the study: "In our study we identified two proteins related to risk factors for the complex genetic eye disease AMD. In addition, for the first time, we were able to map the exact genomic sites of these proteins and found that they operate in a region previously identified as related to risk factors for AMD. Our findings provide new insight into a previously unsolved issue: the functions and mode of operation of genomic sequences located outside the genes, and how they are involved in complex genetic diseases. We believe that our novel research methodology will enable the identification and mapping of many other genetic mechanisms related to AMD and other complex genetic diseases."
Political orientation can be predicted by measuring brain activation while watching campaign-ads
- Social Sciences
A first-of-its-kind study scanned the brains of dozens of politically involved participants while they watched campaign-ads and speeches by parties from both ends of the political spectrum, just before one of the last rounds of elections. The participants, half right-wing and half left-wing, were scanned using magnetic resonance imaging (fMRI), a method that measures brain activation. Surprisingly, political-dependent differences in the brain response emerged already in early brain regions, such as regions involved in vision and hearing, and in fact the response in these regions was enough to predict an individual's political views.
Great Minds Think Alike
The study was led by Noa Katabi, a research student in the lab of Dr. Yaara Yeshurun in The School of Psychological Sciences and the Sagol School of Neuroscience. The study was published in the Journal of Neuroscience.
During the study, participants watched video-clips, including a neutral (in terms of political characteristics) video-clip and different political campaign-ads and political speeches by politicians from both blocs, Right and Left. The researchers were surprised to discover widespread partisanship-dependent brain activation and synchronization when Right-wing individuals watched the videos of their political bloc, or when Left-wing individuals watched the videos of left-wing politician.
Interestingly, the researchers found that such partisanship-dependent differences in brain synchronization was not limited to "higher" areas of the brain, associated with interpretation and abstract thinking, as was previously found. Rather, these differences occurred already in regions responsible for sight, hearing and even touch.
"This is the first study to show political-dependent brain activity in early sensory and motor areas, and it can be said that at the most basic brain level, rightists and leftists in Israel literally (and not just metaphorically) don't see and hear the same things." Dr. Yaara Yeshurun
Dr. Yaara Yeshurun
Rightists and Leftists Experience Things Differently
"The research clearly showed that the more the subjects were politically aligned with a certain group, the more their brain response was synchronized, including in motor and somatosensory areas, that is, those areas of the brain that are active when we move or feel things with our senses," explains Dr. Yeshurun. "In fact, just by the brain’s response in these primary sensory areas we could tell if a certain individual was left or wight wing. Intriguingly, it was not necessary to examine the activity in 'higher' brain areas - areas that are involved in understanding why a certain character did something, or what that character thinks and feels - to predict participants' political views, it could even be done by examining an area of the brain that is responsible for seeing or hearing.”
The researchers think that this surprising finding is due to the fact that the participants they chose were politically involved, and also due to the timing of the experiment - a few weeks before the elections, when the political atmosphere in Israel was very present and emotional.
"This is the first study to show political-dependent brain activity in early sensory and motor areas, and it can be said that at the most basic brain level, rightists and leftists in Israel literally (and not just metaphorically) don't see and hear the same things. I think that if we try to understand how people who hold opposite political views to ours experience the world, we might be able to conduct a slightly more effective public discussion that can hopefully attenuate the current political polarization,” adds Dr. Yeshurun.
Right or left? "If we try to understand how people who hold opposite political views to ours experience the world, we might be able to conduct a slightly more effective public discussion (…)"
Findings contradict prevalent belief that people on the autism spectrum are 'indifferent to pain'
A new study examined the pain perception among people with autism and found that they experience pain at a higher intensity than the general population and are less adaptable to the sensation. This finding is contrary to the prevalent belief that people with autism are supposedly 'indifferent to pain'. The researchers expressed the hope that the findings of their study will lead to more appropriate treatment on the part of medical staff, caregivers, and parents toward people with autism, who do not always express the experience of pain in the usual way.
The study was funded by the Israel Science Foundation and was led by four researchers: Dr. Tami Bar-Shalita of the Sackler Faculty of Medicine at Tel Aviv University who initiated the study, Dr. Yelena Granovsky of the Technion and Rambam Medical Center, and Prof. Irit Weissman-Fogel and Prof. Eynat Gal of the University of Haifa. This study constitutes a framework for the theses of PhD students Tzeela Hofmann and Mary Klingel-Levy, and three articles based on it have already been published or approved for publishing. The present study has been published in the prestigious PAIN journal.
"We know that self-harm could stem from attempts to suppress pain, and it could be that [people with autism] hurt themselves to activate, unconsciously, a physical mechanism of 'pain inhibits pain'." Dr. Tami Bar-Shalita
Self-harm Not Proof of Indifference to Pain
"Approximately 10% of the general population suffer from sensory modulation dysfunction, which means sensory hypersensitivity at a level that compromises normal daily functioning and quality of life. These people have difficulty, for example, ignoring or adapting to buzzing or flickering of fluorescent lights, humming of air conditioners or fans, or the crunching of popcorn by someone sitting next to them in the cinema," explains Dr. Bar-Shalita.
"In previous studies in the lab we found that these people suffer from pain more than those without sensory modulation dysfunction. Since it is known that sensory modulation dysfunction occurs in people with autism at a rate of 70-90%, it constitutes a criterion for diagnosing autism, and is associated with its severity. We were interested in exploring pain perception in autism, so we asked: do people with autism hurt more than the general population? This question was hardly studied in the lab before we got started."
According to the researchers, for many years the prevalent opinion was that 'people with autism hurt less' or that they were 'indifferent to pain'. Actually, 'indifference to pain' is one of the characteristics presented in the current diagnostic criteria of autism.
The proof of this was, supposedly, their tendency to inflict pain on themselves by self-harm.
Dr. Bar-Shalita: "this assumption is not necessarily true. We know that self-harm could stem from attempts to suppress pain, and it could be that they hurt themselves to activate, unconsciously, a physical mechanism of 'pain inhibits pain'."
"The results of our study indicate that in most cases, the sensitivity to pain of people with autism is higher than that of most of the population, while at the same time they are unsuccessful at effectively suppressing painful stimuli." Dr. Tami Bar-Shalita
Dr. Tami Bar-Shalita
Contributing to Advancement of Personalized Treatment
This study is a laboratory pain study approved by the ethics committee of the academic institutions and Rambam Medical Center. The study included 52 adults with high-functioning autism (HFA) and normal intelligence – hitherto the largest reported sample in the world in studies on pain among people with autism. The study made use of psychophysical tests to evaluate pain, commonly used in the area of pain study. These methods examine the link between stimulus and response, while the researcher, using a computer, controls the duration and intensity of stimulus and the examinee is asked to rank the intensity of the pain felt by him on a scale of 0 to 100.
The findings have proven beyond doubt that people with autism hurt more. Furthermore, their pain suppression mechanism is less effective.
The researchers conducted a variety of measurements, aimed among other things at examining whether the hypersensitivity to pain derives from a sensitized nervous system or from suppression of mechanisms that are supposed to enable adjustment and, over time, reduce the response to the stimulus. They found that in the case of people with autism, it is a combination of the two: an increase of the pain signal along with a less effective pain inhibition mechanism.
Dr. Bar-Shalita concludes: "our study constituted a comprehensive, in-depth study of the intensity of pain experienced by people with autism. The prevalent belief was that they are supposedly 'indifferent to pain', and there are reports that medical and other professional staff treated them accordingly. The results of our study indicate that in most cases, the sensitivity to pain of people with autism is higher than that of most of the population, while at the same time they are unsuccessful at effectively suppressing painful stimuli. We hope that our findings will benefit the professionals and practitioners handling this population and contribute to the advancement of personalized treatment."
In additional articles soon to be published, the researchers have examined the brain activity of people with autism during pain stimuli, and sub-groups within this population concerning their perception of pain.
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.”
In a scientific first, a robot can “smell” using a biological sensor
- Life Sciences
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