Scientists in Japan have made a breakthrough in the fight against cancer using artificial DNA. Lab tests successfully targeted and destroyed human cervical and breast cancer cells, as well as mouse malignant melanoma cells.
Hairpin-shaped DNA interacts with microRNA in cancer cells, activating an immune response.
University of Tokyo researchers have made a breakthrough in the fight against cancer with the use of artificial
Cancer is a disease that affects millions of people globally. Cancer is one of the leading causes of death, with approximately 9.6 million deaths occurring in 2018. It is estimated that one in five men and one in six women will develop cancer in their lifetime.
Cancer is a sadly familiar global health concern and current methods of treatment have their limitations. However, drugs based on nucleic acids — namely DNA and
Nucleic
Oncolytic DNA hairpin pairs (oHPs) are introduced to the cancer cell. When the oHPs encounter the tumor-causing overexpressed microRNA (miRNA), they unravel to connect with the miRNA and each other to form longer DNA strands. These elongated strands then trigger an immune response, the body’s built-in defense mechanism, which inhibits further tumor growth. Credit: 2022 Akimitsu Okamoto
Cancer cells can overexpress, or make too many copies of, certain DNA or RNA molecules, causing them to not function normally. The team created artificial oncolytic (cancer-killing) hairpin DNA pairs called oHPs. These oHPs were triggered to form longer DNA strands when they encountered a short (micro) RNA called miR-21, which is overexpressed in some cancers.
Typically, oHPs don’t form longer strands due to their curved hairpin shape. However, when the artificial oHPs enter a cell and encounter the target microRNA, they open up to combine with it and form a longer strand. This then causes the immune system to recognize the presence of the overexpressed miR-21 as dangerous and activate an innate immune response, which ultimately leads to the death of the cancer cells.
The tests were effective against overexpressed miR-21 found in human cervical cancer-derived cells, human triple-negative breast cancer-derived cells, and mouse malignant melanoma-derived cells. “The formation of long DNA strands due to the interaction between short DNA oHPs and overexpressed miR-21, found by this research group, is the first example of its use as a selective immune amplification response which can target tumor regression, providing a new class of nucleic acid drug candidates with a mechanism that is completely different from known nucleic acid drugs,” said Okamoto.
“The results of this study are good news for doctors, drug discovery researchers, and cancer patients, as we believe it will give them new options for drug development and medication policies. Next, we will aim for drug discovery based on the results of this research, and examine in detail the drug efficacy, toxicity, and potential administration methods.” This research still has many steps to go before a treatment can be made available, but the team is confident in the benefits of nucleic acids for new drug discovery.
Reference: “Oncolytic Hairpin DNA Pair: Selective Cytotoxic Inducer through MicroRNA-Triggered DNA Self-Assembly” by Kunihiko Morihiro, Hiraki Osumi, Shunto Morita, Takara Hattori, Manami Baba, Naoki Harada, Riuko Ohashi and Akimitsu Okamoto, 20 December 2022, Journal of the American Chemical Society. DOI: 10.1021/jacs.2c08974
The study was funded by JST ACT-X, JSPS KAKENHI, an AMED Grant, and the Hitachi Global Foundation.
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Radiation from nail dryers may damage DNA and cause cancer-causing mutations in human cells, a new study has found — and that might have you wondering whether your regular gel mani-pedi is worth the risk.
Some dermatologists say the findings, in a study published January 17 in the journal Nature Communications, aren’t new when it comes toconcerns about ultraviolet, or UV, light from any source. In fact, the results reaffirm the reason why some dermatologists have changed the way they get their gel manicures or have stopped getting them altogether.
“The findings contribute to data already published regarding the harmful effects of (ultraviolet) radiation and show direct cell death and damage to tissue that can lead to skin cancer,” said Dr. Julia Curtis, an assistant professor of dermatology at the University of Utah, who wasn’t involved in the study.
“Tanning beds are listed as carcinogenic and UV nail lamps are mini tanning beds for your nails in order to cure the gel nail,” Curtis said.
A form of electromagnetic radiation, ultraviolet light has a wavelength ranging from 10 to 400 nanometers, according to the UCAR Center for Science Education.
Ultraviolet A light (315 to 400 nanometers), found in sunlight, penetrates the skin more deeply and is commonly used in UV nail dryers, which have become popular over the past decade. Tanning beds use 280 to 400 nanometers, while the spectrum used in nail dryers is 340 to 395 nanometers, according to a news release for the study.
“If you look at the way these devices are presented, they are marketed as safe, with nothing to be concerned about,” said corresponding author Ludmil Alexandrov in the news release. “But to the best of our knowledge, no one has actually studied these devices and how they affect human cells at the molecular and cellular levels until now.” Alexandrov holds dual titles as associate professor of bioengineering and cellular and molecular medicine at the University of California San Diego.
Researchers exposed cells from humans and mice to UV light, finding that a 20-minute session led to 20% to 30% of cells dying. Three consecutive 20-minute exposures made 65% to 70% of the exposed cells die. The remaining cells experienced mitochondrial and DNA damage, resulting in mutations with patterns that have been observed in skin cancer in humans.
The biggest limitation of the study is that exposing cell lines to UV light is different from conducting the study on living humans and animals, said dermatologist Dr. Julie Russak, founder of Russak Dermatology Clinic in New York City. Russak wasn’t involved in the study.
“When we’re doing it (irradiating) inside human hands, there’s definitely a difference,” Russak said. “Most of the UV irradiation is absorbed by the top layer of the skin. When you irradiate cells in the petri dish directly, that’s slightly different. You don’t have any protection from the skin, from corneocytes or the top layers. It’s also very direct UVA irradiation.”
But this study, taken together with previous evidence — such as case reports of people developing squamous cell carcinomas, the second most common form of skin cancer, in association with UVA dryers — means we should “definitely think harder about just exposing our hands and our fingers to UVA light without any protection,” said Dr. Shari Lipner, an associate professor of clinical dermatology and director of the nail division at the NewYork-Presbyterian Hospital/Weill Cornell Medical Center. Lipner wasn’t involved in the study.
If you’re concerned about gel manicures but don’t want to give them up, there are some precautions you can take to mitigate the risks.
“Apply broad spectrum sunblock that contains zinc and titanium around the nails, and wear UV gloves with the fingertips cut off when it is time to cure your nails,” said Curtis, who doesn’t get gel manicures. “I would recommend alternatives to gel nails, such as the new wraps that are available online.” (Gel nail wraps or strips are stick-on gel nail products that don’t always require being set by UV nail dryers.)
Some salons use LED lights, which “are thought to emit either no UV light or much, much lower amounts,” Lipner said.
Lipner gets regular manicures — which typically last her seven to 10 days — not in an effort to avoid UV light but ratherbecause she doesn’t like the nail-thinning acetone soaking involved with gel manicures.
“Regular manicures are just dried in the air,” she added. “Gel manicures have to be curated or sealed, and the polymers in the polish have to be activated, so that can only be done with the UVA lights.”
If you have regularly gotten gel manicures, Lipner recommends seeing a board-certified dermatologist who can examine your skin for any skin cancer precursors and treat them before they become a serious problem. (Ultraviolet light can also age the skin, showing up as sunspots and wrinkles, she said.)
There isn’t enough data for experts to weigh in on how often people can get gel manicures without putting themselves at risk, Lipner said. But Curtis recommended saving them for special occasions.
Russak doesn’t get gel manicures very often but uses sunscreen and gloves when she does, she said. Applying serums rich in antioxidants, such as vitamin C, beforehand might also help, she added.
“As a dermatologist, I change gloves probably three, four times with just one patient. And with a regular nail polish, after three, four glove changes, the nail polish is gone,” Russak added. “The gel manicure definitely has a much better longevity, but is it really worth the risk of photoaging and development of skin cancer? Probably not.”
People with a history of skin cancers or who are more photosensitive due to fairer skin or albinism, medications or immunosuppression should be more careful about taking precautions, experts said. Whether or not you are at higher risk, however, the dermatologists CNN spoke with urged caution.
“Unfortunately, full protection is not possible, so my best recommendation is to avoid these dryers altogether,” Zeichner said.
Researchers have developed a new machine-learning model to detect cancers that are in their early stages of disease by examining DNA fragments from cancer cells in the blood.
A University of Wisconsin–Madison research team was able to detect cancer in the bloodstream in most of the samples tested, it said.
Muhammed Murtaza, professor of surgery at the UW School of Medicine and Public Health based in Madison, Wisconsin, led the study, which was published recently in Science Translational Medicine, a medical journal from the American Association for the Advancement of Science, according to the study’s press release.
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“We’re incredibly excited to discover that early detection and monitoring of multiple cancer types are potentially feasible using such a cost-effective approach,” said Murtaza in the press release.
Earlier detection of many cancers will lead to better outcomes for patients, the release noted.
“We’re incredibly excited to discover that early detection and monitoring of multiple cancer types are potentially feasible using such a cost-effective approach,” says the lead author of a new study. (iStock)
Although other scientists are also developing blood tests to detect cancer earlier, the present technology has limitations, such as cost and the “sensitivity” of the test.
Sensitivity, in this case, refers to the ability of the test to correctly detect the presence of cancer, according to the Centers for Disease Control and Prevention (CDC).
How is the test done?
When cells die as part of the body’s natural process of cell turnover, fragments of DNA are released outside the cells. These start to circulate in the bloodstream — namely, the plasma, which is the liquid portion of the blood, according to the researchers.
“It should be focused on patients that have significant family histories or personal risk factors, or that have genetic syndromes that are associated with getting multiple cancers.”
The research team hypothesized that cancer cells have DNA fragments that are different from healthy cells, specifically where the DNA strands “break.” Nucleotides, which are the “building blocks of DNA,” surround these break points.
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The research team used a special technique that the study named Genome-wide AnaLYsis of FRagment Ends — or GALYFRE — to analyze the “cell-free” DNA from 521 samples.
For a new study, a research team at the University of Wisconsin-Madison also “sequenced” data from an additional 2,147 samples from two groups of people: healthy individuals — and patients with 11 different cancer types. (iStock)
The team also “sequenced” data from an additional 2,147 samples from two groups of people: healthy individuals, and patients with 11 different cancer types.
“Sequencing DNA means determining the order of the four chemical building blocks — called “bases” — that make up the DNA molecule,” according to the National Institutes of Health’s website on human genome research.
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“The sequence tells scientists the kind of genetic information that is carried in a particular DNA segment.”
The research team then used these analyses to develop a metric that could reflect the proportion of DNA molecules that were from cancer in each sample.
Machine-learning model
They combined this measure with the genetic information found on the DNA fragments to develop a model that trains a machine to compare DNA fragments from healthy cells to DNA fragments from different types of cancer cells.
“The sequence tells scientists the kind of genetic information that is carried in a particular DNA segment.”
This model differentiated people with cancer at any stage of their diagnosis from people without cancer 91% of the time.
It also “accurately identified samples from patients with stage 1 cancer in 87% of cases, suggesting it holds promise for detecting cancer in early stages,” per the release.
The research team hopes to perform more clinical studies to validate the blood test for specific cancers, such as pancreatic cancer and breast cancer. (iStock)
The study, however promising, notes that more research is needed to apply GALYFRE’s use for patients in different age groups and those who have multiple medical problems.
Refinement needed for future
The research team hopes to perform more clinical studies to validate the blood test for specific cancers, such as pancreatic cancer and breast cancer.
“One direction we are taking is refining GALYFRE to make it even more accurate for some patients who are at risk of developing specific types of cancers,” Murtaza noted in the release.
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His team is also looking to see if this technology can be used not only for earlier detection of cancers, but also for monitoring how chemotherapy patients respond to cancer treatments.
Researchers hope that “this work will lead to a blood test for cancer detection and monitoring that will be available clinically in the next 2-5 years for at least some conditions.”
“I find that using cell-free DNA and a liquid biopsy will be most useful for patients with a known cancer diagnosis and [for] post treatment to monitor for disease recurrence — avoiding the need for [high-risk] biopsy,” Dr. Oren N. Gottfried, professor at Duke University School of Medicine in Durham North Carolina, told Fox News Digital.
“This is particularly true with brain cancer, where each brain biopsy includes considerable risk,” added Gottfried, who is also a neurosurgeon.
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“In general as a screening tool, I feel it should be focused on patients that have significant family histories or personal risk factors, or that have genetic syndromes that are associated with getting multiple cancers.”
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Murtaza of the UW School of Medicine and Public Health hopes with further research and development that “this work will lead to a blood test for cancer detection and monitoring that will be available clinically in the next 2-5 years for at least some conditions — and ultimately be accessible for patients with limited health care resources in the U.S. and around the world,” he said in the news release.
Researchers at UC San Diego studied the UV light-emitting devices used to cure gel manicures, and found that the chronic use of these nail polish drying machines is damaging to human cells. Credit: David Baillot/ UC San Diego Jacobs School of Engineering
The ultraviolet nail polish drying devices used to cure gel manicures may pose more of a public health concern than previously thought. Researchers at the University of California San Diego studied these ultraviolet (UV) light-emitting devices, and found that their use leads to cell death and cancer-causing mutations in human cells.
The devices are a common fixture in nail salons, and generally use a particular spectrum of UV light (340-395nm) to cure the chemicals used in gel manicures. While tanning beds use a different spectrum of UV light (280-400nm) that studies have conclusively proven to be carcinogenic, the spectrum used in the nail dryers has not been well studied.
“If you look at the way these devices are presented, they are marketed as safe, with nothing to be concerned about,” said Ludmil Alexandrov, a professor of bioengineering as well as cellular and molecular medicine at UC San Diego, and corresponding author of the study published on January 17 in the journal
Maria Zhivagui, a postdoctoral scholar in the Alexandrov Lab and first author of the study, prepares human cells in Petri dishes for exposure to the manicure curing device. Credit: David Baillot/ UC San Diego Jacobs School of Engineering
Exposure to the UV light also caused mitochondrial and
“When I was doing my PhD, I started hearing about gel manicures, which last longer than normal polish. I was interested in trying out gel nail polish, particularly in the setting of working in an experimental lab where I frequently put gloves on and off, to maintain a presentable appearance,” said Zhivagui. “So I started using gel manicures periodically for several years. Once I saw the effect of radiation emitted by the gel polish drying device on cell death and that it actually mutates cells even after just one 20-minute session, I was surprised. I found this to be very alarming, and decided to stop using it.”
Studying their effect on human cells
The idea to study these particular devices came to Alexandrov in a dentist’s office, of all places. As he waited to be seen, he read a magazine article about a young beauty pageant contestant who was diagnosed with a rare form of skin cancer on her finger.
“I thought that was odd, so we began looking into it, and noticed a number of reports in medical journals saying that people who get gel manicures very frequently– like pageant contestants and estheticians– are reporting cases of very rare cancers in the fingers, suggesting that this may be something that causes this type of cancer,” said Alexandrov. “And what we saw was that there was zero molecular understanding of what these devices were doing to human cells.”
Three cell types were exposed to two different conditions: acute exposure and chronic exposure to the UV light device, pictured here. Credit: David Baillot/ UC San Diego Jacobs School of Engineering
To conduct the study, Zhivagui exposed the three cell types to two different conditions: acute exposure and chronic exposure to the UV light device. Under acute exposure, Petri dishes containing one of the cell types were placed in one of these UV curing machines for a 20-minute session. They were then taken out for an hour to repair or return to their steady state, and then given one more 20-minute exposure. Under chronic exposure, the cells were placed under the machine for 20 minutes a day for three days.
Cell death, damage and DNA mutations were seen under both conditions, with an elevation of reactive oxygen species molecules– known to cause DNA damage and mutations– and mitochondrial dysfunction in the cells. Genomic profiling revealed higher levels of somatic mutations in the irradiated cells, with patterns of mutations ubiquitously present in melanoma patients.
Is the risk worth the reward?
This data in human cells, coupled with a number of prior reports of cancers in people who get gel manicures very frequently, paint a picture of a purely cosmetic procedure that is riskier than previously believed. But is getting a gel manicure once a year really cause for concern, or should only those who get this done on a very regular basis be worried? Further studies are needed to quantify any increased risk of cancer and at what frequency of use, but with plenty of alternatives to this cosmetic procedure, the risk may not be worth it to some consumers.
“Our experimental results and the prior evidence strongly suggest that radiation emitted by UV-nail polish dryers may cause cancers of the hand and that UV-nail polish dryers, similar to tanning beds, may increase the risk of early-onset skin cancer,” they write. “Nevertheless, future large-scale epidemiological studies are warranted to accurately quantify the risk for skin cancer of the hand in people regularly using UV-nail polish dryers. It is likely that such studies will take at least a decade to complete and to subsequently inform the general public. ”
Though other consumer products use UV light in the same spectrum– including the tool used to cure dental fillings and some hair removal treatments– the researchers note that the regularity of use, plus the entirely cosmetic nature of nail dryers, sets them apart.
Reference: “DNA damage and somatic mutations in mammalian cells after irradiation with a nail polish dryer” by Maria Zhivagui, Areebah Hoda, Noelia Valenzuela, Yi-Yu Yeh, Jason Dai, Yudou He, Shuvro P. Nandi, Burcak Otlu, Bennett Van Houten and Ludmil B. Alexandrov, 17 January 2023, Nature Communications. DOI: 10.1038/s41467-023-35876-8
Since arriving on the market around 2010, gel manicures have become a staple in nail salons across the US and many parts of the world, and it’s easy to see why. Compared to traditional nail polish, gel variants are more resilient to damage and smudging, and they retain their shine until you remove the polish from your fingernails. Best of all, if you’re the impatient sort, you don’t need to wait an hour or more for a gel manicure to dry. Those benefits all come courtesy of the way the polish cures. Instead of waiting for a gel polish to dry naturally, you place your hands under a UV light, which activates the chemicals inside the gel, causing it to harden.
While the dangers of UV light — particularly in tanning settings — are well-known, before this week scientists had not studied how the ultraviolet lights used to cure gel polishes might affect human skin. You might think what we know about tanning beds applies here, but the devices used by nail salons emit a different spectrum of ultraviolet light. A group of researchers from the decided to study the devices after reading an article about a beauty pageant contestant who was diagnosed with a rare form of skin cancer.
Using different combinations of human and mouse cells, the researchers found a single 20-minute session with an ultraviolet nail polish dryer led to as many as 30 percent of the cells in a petri dish dying. Three consecutive 20-minute sessions saw 65 to 70 percent of the exposed cells dying off. Among the remaining cells, the researchers saw evidence of mitochondrial and DNA damage, in addition to mutations that have been seen in skin cancer patients.
“Our experimental results and the prior evidence strongly suggest that radiation emitted by UV-nail polish dryers may cause cancers of the hand and that UV-nail polish dryers, similar to tanning beds, may increase the risk of early-onset skin cancer,” the researchers write in a study published in the journal on Tuesday. They warn that a longer epidemiological study is needed before they can conclusively say the use of UV drying devices leads to an increased risk of skin cancer, adding “it is likely that such studies will take at least a decade to complete and to subsequently inform the general public.”
You might think the advice here is to avoid UV dryers, but it’s not so simple. Gel manicures have become an industry standard for a reason. For many people, regular nail polish starts to chip off after a day or so, making a traditional manicure often not worth the time, money or effort.
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The ultraviolet nail polish drying devices used to cure gel manicures may pose more of a public health concern than previously thought. Researchers at the University of California San Diego have studied these ultraviolet (UV) light emitting devices, and found that their use leads to cell death and cancer-causing mutations in human cells.
The devices are a common fixture in nail salons, and generally use a particular spectrum of UV light (340-395nm) to cure the chemicals used in gel manicures. While tanning beds use a different spectrum of UV light (280-400nm) that studies have conclusively proven to be carcinogenic, the spectrum used in the nail dryers has not been well studied.
“If you look at the way these devices are presented, they are marketed as safe, with nothing to be concerned about,” said Ludmil Alexandrov, a professor of bioengineering as well as cellular and molecular medicine at UC San Diego, and corresponding author of the study published in Nature Communications. “But to the best of our knowledge, no one has actually studied these devices and how they affect human cells at the molecular and cellular levels until now.”
Using three different cell lines—adult human skin keratinocytes, human foreskin fibroblasts, and mouse embryonic fibroblasts—the researchers found that the use of these UV emitting devices for just one 20-minute session led to between 20 and 30 percent cell death, while three consecutive 20-minute exposures caused between 65 and 70 percent of the exposed cells to die.
Exposure to the UV light also caused mitochondrial and DNA damage in the remaining cells and resulted in mutations with patterns that can be observed in skin cancer in humans.
“We saw multiple things: first, we saw that DNA gets damaged,” said Alexandrov. “We also saw that some of the DNA damage does not get repaired over time, and it does lead to mutations after every exposure with a UV-nail polish dryer. Lastly, we saw that exposure may cause mitochondrial dysfunction, which may also result in additional mutations. We looked at patients with skin cancers, and we see the exact same patterns of mutations in these patients that were seen in the irradiated cells.”
The researchers caution that while the results show the harmful effects of the repeated use of these devices on human cells, a long-term epidemiological study would be required before stating conclusively that using these machines leads to an increased risk of skin cancers. However, the results of the study were clear: The chronic use of these nail polish drying machines is damaging to human cells.
Maria Zhivagui, a postdoctoral scholar in the Alexandrov Lab and first author of the study, used to be a fan of gel manicures herself, but has sworn off the technique after seeing the results.
“When I was doing my Ph.D., I started hearing about gel manicures, which last longer than normal polish. I was interested in trying out gel nail polish, particularly in the setting of working in an experimental lab where I frequently put gloves on and off, to maintain a presentable appearance,” said Zhivagui. “So I started using gel manicures periodically for several years. Once I saw the effect of radiation emitted by the gel polish drying device on cell death and that it actually mutates cells even after just one 20-minute session, I was surprised. I found this to be very alarming, and decided to stop using it.”
Studying their effect on human cells
The idea to study these particular devices came to Alexandrov in a dentist’s office, of all places. As he waited to be seen, he read a magazine article about a young beauty pageant contestant who was diagnosed with a rare form of skin cancer on her finger.
“I thought that was odd, so we began looking into it, and noticed a number of reports in medical journals saying that people who get gel manicures very frequently—like pageant contestants and estheticians—are reporting cases of very rare cancers in the fingers, suggesting that this may be something that causes this type of cancer,” said Alexandrov. “And what we saw was that there was zero molecular understanding of what these devices were doing to human cells.”
To conduct the study, Zhivagui exposed the three cell types to two different conditions: acute exposure and chronic exposure to the UV light device. Under acute exposure, Petri dishes containing one of the cell types were placed in one of these UV curing machines for a 20-minute session. They were then taken out for an hour to repair or return to their steady state, and then given one more 20-minute exposure. Under chronic exposure, the cells were placed under the machine for 20 minutes a day for three days.
Cell death, damage and DNA mutations were seen under both conditions, with an elevation of reactive oxygen species molecules—known to cause DNA damage and mutations—and mitochondrial dysfunction in the cells. Genomic profiling revealed higher levels of somatic mutations in the irradiated cells, with patterns of mutations ubiquitously present in melanoma patients.
Is the risk worth the reward?
This data in human cells, coupled with a number of prior reports of cancers in people who get gel manicures very frequently, paint a picture of a purely cosmetic procedure that is riskier than previously believed. But is getting a gel manicure once a year really cause for concern, or should only those who get this done on a very regular basis be worried? Further studies are needed to quantify any increased risk of cancer and at what frequency of use, but with plenty of alternatives to this cosmetic procedure, the risk may not be worth it to some consumers.
“Our experimental results and the prior evidence strongly suggest that radiation emitted by UV-nail polish dryers may cause cancers of the hand and that UV-nail polish dryers, similar to tanning beds, may increase the risk of early-onset skin cancer,” they write. “Nevertheless, future large-scale epidemiological studies are warranted to accurately quantify the risk for skin cancer of the hand in people regularly using UV-nail polish dryers. It is likely that such studies will take at least a decade to complete and to subsequently inform the general public.”
Though other consumer products use UV light in the same spectrum—including the tool used to cure dental fillings and some hair removal treatments—the researchers note that the regularity of use, plus the entirely cosmetic nature of nail dryers, sets them apart.
More information:
Maria Zhivagui et al, DNA damage and somatic mutations in mammalian cells after irradiation with a nail polish dryer, Nature Communications (2023). DOI: 10.1038/s41467-023-35876-8
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Tens of thousands of demonstrators braved rainy weather Saturday night to gather at Tel Aviv’s Habima Square for protests against Prime Minister Benjamin Netanyahu’s new government and its plans for sweeping changes to Israel’s justice system.
Police estimated some 80 thousand people rallied in the square and surrounding streets, with many traveling to Tel Aviv from around the country on hired buses. Demonstrations were also held in Jerusalem and Haifa.
Despite police warnings of possible violence and National Security Minister Itamar Ben Gvir’s call for police to crack down on any unrest, the demonstrations ended largely peacefully, with only a few sporadic clashes between protesters and cops.
Roads near Habima Square were shuttered throughout the rally, as police deployed in force in the city center to maintain order.
Among those in attendance were former opposition leader Tzipi Livni, former prime minister Ehud Barak, National Unity party leader and former defense minister Benny Gantz, former IDF chief Gadi Eisenkot (National Unity) and Labor party leader Merav Michaeli.
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The demonstration marked the second week that opponents of Netanyahu’s government took to the streets, protesting Justice Minister Yariv Levin’s proposals to shake up the judiciary by severely curbing the High Court of Justice’s judicial review powers and cementing political control over the appointment of judges.
Thousands of people protest against the Israeli government at Habima Square in Tel Aviv, on January 14, 2023. (Yonatan Sindel/Flash90)
Taking the stage in Tel Aviv, Livni vowed that “nobody will be above the law, not even the prime minister… Together we will protect the state, because it is for all of us.”
Addressing lawmakers advancing the controversial judicial overhaul, she said “history will not forget.”
The chair of the Movement for Quality Government in Israel, Eliad Shraga, told the crowd: “Always remember that we prefer the cold and the rain of liberal democracy than the heat and hell of a fascist dictatorship.”
Shraga called on President Isaac Herzog to declare Netanyahu as unfit to serve as prime minister. He said the new government aims to “change the DNA of the State of Israel,” transforming it from a secular state to a religious fundamentalist state that harms the rights of women and the LGBTQ community.
People protest against the Israeli government in Tel Aviv, on January 14, 2023 (Tomer Neuberg/Flash90)
Former Supreme Court justice Ayala Procaccia said “something is deeply broken in our social pact, in the basic framework of rules agreed upon throughout the country’s history.
“We are at the start of a new era in which democracy has a new definition: not a value-based democracy but a fractured democracy leaning entirely on ‘the will of the voter,’ which no longer gives any weight to other democratic principles.”
Procaccia said the public “will not accept…the destruction of the values that are the basis of our system… We are at a fateful moment of decision for the moral future of Israel.”
Israeli protesters attend a rally against Prime Minister Benjamin Netanyahu’s new government in the coastal city of Tel Aviv on January 14, 2023 (AHMAD GHARABLI / AFP)
With the rally ongoing, several hundred protesters began marching down Ibn Gabirol Street, escorted by police down the road, which was blocked for vehicular traffic.
“No democracy without the High Court,” the marchers chanted with drummers. Motorists on nearby roads cheered and honked in support of the march, despite being caught in a jam.
Police blocked the entrance to the Ayalon Highway, preventing protesters from entering and disrupting traffic there.
Later in the evening, police scuffled with some anti-government protesters, as around 200 attempted to enter the highway and block it. The crowd initially tried to enter from a junction, and then via the underground parking lot of the Azrieli mall. Police said officers managed to push the crowd back.
Protesters clash with police after attending a demonstration against the Benjamin Netanyahu’s government, in Tel Aviv, on January 14, 2023. (Yonatan Sindel/Flash90)
In Haifa, hundreds of people gathered at the Horev Center in Haifa, while thousands protested outside the President’s Residence in the capital, bundled in winter coats and hats, waving Israeli flags and placards and calling for the president, Isaac Herzog, to emerge.
Several hundred of the Jerusalem protestors marched toward Azza Road, where Netanyahu’s temporary residence is located. Police placed roadblocks to prevent crowds from nearing the premier’s home.
The crowd, including families with young children, kippah wearers, and older residents, shouted, “My country has three branches of government, three!”
עזה פינת ארלוזורוב, הפגנה מהרגועות שראינו בואכה ימי בלפור pic.twitter.com/xXM1B58X2r
— Haim Goldich | חיים גולדיטש (@HGoldich) January 14, 2023
A police officer was also seen assaulting a protester during the demonstration outside the President’s Residence. Israel Police chief Kobi Shabtai’s office told the Kan public broadcaster that the incident was being investigated.
It was unclear what preceded the violence.
ההפגנה נגד הממשלה: שוטר תועד מכה מפגין בפניו במחאה מול בית הנשיא בירושלים | לידיעה המלאה >>> https://t.co/C5C7RLOAfw@SuleimanMas1 (צילום: פרי ג׳רוזלם) pic.twitter.com/aO3xQ7XLwu
— כאן חדשות (@kann_news) January 14, 2023
Ahead of the Tel Aviv rally, the chief of police’s Tel Aviv District, Ami Eshed, said that there was no change in policy.
“Our main goal is that everyone who comes to the demonstration will be able to arrive in an orderly manner and leave here in an orderly and safe manner,” Eshed was quoted by the Ynet news site as saying during a tour of the square prior to the event’s start.
“Our only goal is to deal with people who are committing vandalism or violence. We don’t deal with things that are trivial,” he told officers.
According to the Haaretz daily, police placed security around the home of Knesset Speaker Amir Ohana (Likud), who lives near Habima Square.
Israelis protest against Benjamin Netanyahu’s government, in Tel Aviv, on January 14, 2023. (Jack Guez/AFP)
Sheltering from the rain under a tree, Lorna from Tel Aviv said she came to the protest to try to ensure her grandchildren’s future.
“I feel like we are living in the beginnings of a dystopian state,” she said. “I am seeing the end of democracy and I feel personally threatened.”
Reut from Tel Aviv came to the protest as part of a three-generation delegation from her family. “We are starting to not recognize our own country,” she said. “And that’s an understatement.”
Hadas traveled from Ganei Tikva. “We don’t like what’s happening here,” she said. “I don’t know if [protesting] will make a difference. But if we don’t do something then for sure nothing will change,” she added.
Saturday’s rallies were being backed by top groups that led protests against Netanyahu in 2020: Ein Matzav (No Way), Crime Minister and the Black Flags. They have also been endorsed by other organizations, including the Association for LGBTQ Equality in Israel, the Movement for Quality Government and the Kibbutz Movement.
“Bougie, wake up, the house is burning,” the demonstrators chanted, referring to the president by his nickname.“Bougie, Bougie, wake up, the public is worth more.”
Israelis protest against Benjamin Netanyahu’s government, outside the President’s Residence in Jerusalem, on January 14, 2023. (Jessica Steinberg/Times of Israel)
Ahead of the rallies, ex-police chief Moshe Karadi said law enforcement had information that right-wing activists intended to plant agitators at the protests.
“Elements from the other side sometimes plant rioters in demonstrations for the sake of provocation and there is information on this matter in this demonstration as well,” Kan news cited Karadi as saying at a conference in Beersheba.
He downplayed concerns of potential unrest among the demonstrators, saying it was “fake news from certain elements.”
Despite the warnings that the protest may attract right-wing agitators, there were no reports of violence.
Two teens wearing scarves marking them out as fans of the Beitar Jerusalem soccer team, known for its right-wing fans, attempted to provoke a reaction in Tel Aviv.
“Only Ben Gvir,” one teen repeatedly shouted, referring to National Security Minister Itamar Ben Gvir, leader of the far-right Otzma Yehudit party. “Stupid boy,” responded one older lady as the rest of the crowd ignored him.
Israelis protest against Benjamin Netanyahu’s government, in Tel Aviv, on January 14, 2023. (Yonatan Sindel/Flash90)
On Friday, National Unity party leader Benny Gantz had urged Israelis from across the political spectrum to attend the Tel Aviv demonstration.
“I call on the entire Israeli public, from left to right, to come to protest for safeguarding Israeli democracy. Making your voice heard at this time is a civic duty of the highest importance and not ‘civil disobedience’ as those trying to suppress the demonstration claim,” said Gantz, who previously served as defense minister and IDF chief.
Netanyahu, meanwhile, brushed off criticism of the proposed judicial changes a day after Supreme Court Chief Justice Esther Hayut warned their enactment would deal a “fatal blow” to the country’s democratic character.
Thousands of people protest against the Israeli government at Habima Square in Tel Aviv, on January 14, 2023. (Yonatan Sindel/Flash90)
“We discussed this before the elections and we received a clear mandate from the public for this,” Netanyahu asserted in a Friday video. “I suggest everyone calm down and enter into a substantive discussion.”
“When they say that the smallest reform is the destruction of democracy, this is not only a false claim, it also does not allow for the possibility to reach understandings… through substantive dialogue in the Knesset,” Netanyahu added.
Critics of the plans, which include top current and former judicial and legal officials as well as Netanyahu’s political rivals, say Levin’s reforms would put basic civil and minority rights at risk by severely limiting the top court’s authority to strike down laws and government decisions. Proponents of the changes argue that the courts have assumed excessive powers and issued rulings that defy the will of the voters.
Along with Gantz, a number of other politicians were expected to attend the demonstration in Tel Aviv. Opposition leader Yair Lapid said Thursday that he would not join the protest after being told that he and Gantz would not be allowed to address the crowd.
Israelis protest against Benjamin Netanyahu’s government, in Tel Aviv, on January 14, 2023. (Tomer Neuberg/Flash90)
Tel Aviv Mayor Ron Huldai said Friday that he would be in attendance and called on anyone “who cares about the State of Israel and its democratic character” to be there.
“If there is a water cannon, I will stand in front of it,” Huldai told Channel 12 news, amid calls by National Security Minister Itamar Ben Gvir for police to take a harder line against protesters. “To protest is a cornerstone of democracy,” the mayor added.
According to Kan and the Ynet news site, police have barred protesters from marching or blocking roads as conditions for authorizing the rally in Tel Aviv. Several marches were held during last week’s protest, during which some demonstrators also briefly blocked a major highway.
Channel 12 news reported that some protesters were planning to march toward the Azrieli shopping center despite the police ban, and to block roads — which could lead to conflict with officers.
(A–C) Brightfield images of human iPSCs (A). iPSC differentiated into neural rosettes (B) and N2 cells (C) demonstrating typical morphology. (D) Human iPSCs demonstrate normal karyotypes. (E) Human N2 cells express paired box 6 (PAX6), a neural marker. (F) Human N3 cells express glial fibrillary acidic protein (GFAP), a glial marker. (G–I) Brightfield images of chimpanzee iPSCs (G). iPSC differentiated into neural rosettes (H) and N2 cells (I) demonstrating typical morphology. (J) Chimpanzee iPSCs demonstrate normal karyotypes. (K) Chimpanzee N2 cells express PAX6. (L) Chimpanzee N3 cells express GFAP. (M) Percentage of cells in scRNA-seq expressing genes that are markers for the cell cycle or telencephalon and neuronal cell types. Human and chimpanzee N2 and N3 cells show comparable marker expression for radial glia and telencephalon. For example, 50%–90% of cells expressed FOXG1, a marker of the telencephalon. (N and O) Coverage (counts per million [CPM]) of H3K27ac ChIP-seq reads at HARs, sorted by maximum CPM, in human (N) and chimpanzee (O) N2 cells. (P) Human and chimpanzee N2 H3K27ac TF footprints are largely concordant, but some TF families with LIM, POU, and homeodomains show species-biased enrichment. Select TFs expressed in NPCs and with large differences in q value between species are labeled. Credit: Neuron (2023). DOI: 10.1016/j.neuron.2022.12.026
Humans and chimpanzees differ in only one percent of their DNA. Human accelerated regions (HARs) are parts of the genome with an unexpected amount of these differences. HARs were stable in mammals for millennia but quickly changed in early humans. Scientists have long wondered why these bits of DNA changed so much, and how the variations set humans apart from other primates.
Now, researchers at Gladstone Institutes have analyzed thousands of human and chimpanzee HARs and discovered that many of the changes that accumulated during human evolution had opposing effects from each other.
“This helps answer a longstanding question about why HARs evolved so quickly after being frozen for millions of years,” says Katie Pollard, Ph.D., director of the Gladstone Institute of Data Science and Biotechnology and lead author of the new study published today in Neuron. “An initial variation in a HAR might have turned up its activity too much, and then it needed to be turned down.”
The findings, she says, have implications for understanding human evolution. In addition—because she and her team discovered that many HARs play roles in brain development—the study suggests that variations in human HARs could predispose people to psychiatric disease.
“These results required cutting-edge machine learning tools to integrate dozens of novel datasets generated by our team, providing a new lens to examine the evolution of HAR variants,” says Sean Whalen, Ph.D., first author of the study and senior staff research scientist in Pollard’s lab.
Enabled by machine learning
Pollard discovered HARs in 2006 when comparing the human and chimpanzee genomes. While these stretches of DNA are nearly identical among all humans, they differ between humans and other mammals. Pollard’s lab went on to show that the vast majority of HARs are not genes, but enhancers— regulatory regions of the genome that control the activity of genes.
More recently, Pollard’s group wanted to study how human HARs differ from chimpanzee HARs in their enhancer function. In the past, this would have required testing HARs one at a time in mice, using a system that stains tissues when a HAR is active.
Instead, Whalen input hundreds of known human brain enhancers, and hundreds of other non-enhancer sequences, into a computer program so that it could identify patterns that predicted whether any given stretch of DNA was an enhancer. Then he used the model to predict that a third of HARs control brain development.
“Basically, the computer was able to learn the signatures of brain enhancers,” says Whalen.
Knowing that each HAR has multiple differences between humans and chimpanzees, Pollard and her team questioned how individual variants in a HAR impacted its enhancer strength. For instance, if eight nucleotides of DNA differed between a chimpanzee and human HAR, did all eight have the same effect, either making the enhancer stronger or weaker?
“We’ve wondered for a long time if all the variants in HARs were required for it to function differently in humans, or if some changes were just hitchhiking along for the ride with more important ones,” says Pollard, who is also chief of the division of bioinformatics in the Department of Epidemiology and Biostatistics at UC San Francisco (UCSF), as well as a Chan Zuckerberg Biohub investigator.
Validation of an active HAR enhancer regulating ROCK22xHAR. Credit: Neuron (2023). DOI: 10.1016/j.neuron.2022.12.026
To test this, Whalen applied a second machine learning model, which was originally designed to determine if DNA differences from person to person affect enhancer activity. The computer predicted that 43 percent of HARs contain two or more variants with large opposing effects: some variants in a given HAR made it a stronger enhancer, while other changes made the HAR a weaker enhancer.
This result surprised the team, who had expected that all changes would push the enhancer in the same direction, or that some “hitchhiker” changes would have no impact on the enhancer at all.
Measuring HAR strength
To validate this compelling prediction, Pollard collaborated with the laboratories of Nadav Ahituv, Ph.D., and Alex Pollen, Ph.D., at UCSF. The researchers fused each HAR to a small DNA barcode. Each time a HAR was active, enhancing the expression of a gene, the barcode was transcribed into a piece of RNA. Then, the researchers used RNA sequencing technology to analyze how much of that barcode was present in any cell—indicating how active the HAR had been in that cell.
“This method is much more quantitative because we have exact barcode counts instead of microscopy images,” says Ahituv. “It’s also much higher throughput; we can look at hundreds of HARs in a single experiment.”
When the group carried out their lab experiments on over 700 HARs in precursors to human and chimpanzee brain cells, the data mimicked what the machine learning algorithms had predicted.
“We might not have discovered human HAR variants with opposing effects at all if the machine learning model hadn’t produced these startling predictions,” said Pollard.
Implications for understanding psychiatric disease
The idea that HAR variants played tug-of-war over enhancer levels fits in well with a theory that has already been proposed about human evolution: that the advanced cognition in our species is also what has given us psychiatric diseases.
“What this kind of pattern indicates is something called compensatory evolution,” says Pollard. “A large change was made in an enhancer, but maybe it was too much and led to harmful side effects, so the change was tuned back down over time—that’s why we see opposing effects.”
If initial changes to HARs led to increased cognition, perhaps subsequent compensatory changes helped tune back down the risk of psychiatric diseases, Pollard speculates. Her data, she adds, can’t directly prove or disprove that idea. But in the future, a better understanding of how HARs contribute to psychiatric disease could not only shed light on evolution, but on new treatments for these diseases.
“We can never wind the clock back and know exactly what happened in evolution,” says Pollard. “But we can use all these scientific techniques to simulate what might have happened and identify which DNA changes are most likely to explain unique aspects of the human brain, including its propensity for psychiatric disease.”
More information:
Sean Whalen et al, Machine learning dissection of human accelerated regions in primate neurodevelopment, Neuron (2023). DOI: 10.1016/j.neuron.2022.12.026
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New way of using DNA to kill cancer cells could pave the way for a cure, scientists say
University of Tokyo scientists may have paved a way to use DNA to cure cancer
Study author Professor Akimitsu Okamoto says their research is ‘good news’
It uses a hair clip shaped, cancer-killing DNA, which is injected into cancer cells
By Oliver Price For Mailonline
Published: | Updated:
A new way of using DNA to kill cancer cells which could pave the way for a cure for the disease has been created by scientists.
Professor Akimitsu Okamoto from the University of Tokyo and an author of the study, has said the research is ‘good news’ and will open up new options for cancer treatments.
The method targets human cervical cancer and breast cancer-derived cells, as well as malignant melanoma cells in mice.
It uses a pair of hair clip shaped, cancer-killing DNA which are injected into cancer cells.
Professor Akimitsu Okamoto (pictured) from the University of Tokyo, has a new way of using DNA to kill cancer cells which could pave the way for a cure said the research is ‘good news’ and will open up new options for cancer treatments
The method created by scientists at the University of Tokyo (pictured) targets human cervical cancer and breast cancer-derived cells, as well as malignant melanoma cells in mice
When they were injected into them, they connected to molecules called microRNA which are overproduced in certain cancers.
Once connected to the microRNA they unravelled and formed longer chains of DNA which created an immune response.
The immune system recognised the overproduced microRNA cells as dangerous, which activated a natural immune response which killed the cancer cells.
The Japanese research team say their method is different from existing ones and could herald in a new era of breakthrough cancer drugs.
Prof Okamoto said: ‘The results of this study are good news for doctors, drug discovery researchers and cancer patients, as we believe it will give them new options for drug development and medication policies.
‘Next, we will aim for drug discovery based on the results of this research, and examine in detail the drug efficacy, toxicity and potential administration methods.’
He added: ‘We thought that if we can create new drugs that work by a different mechanism of action from that of conventional drugs, they may be effective against cancers that have been untreatable up to now’
The new cancer research uses a pair of hair clip shaped, cancer-killing DNA which are injected into cancer cells
Cancer is sadly a familiar health concern and existing ways of treating it have their limitations, however drugs based on DNA and RNA are expected to help scientists eventually beat it.
This is because DNA and RNA are vital information-carrying molecules that can control the biological function of cells.
They are expected to transform the future of medicine and help cure other hard to treat illnesses caused by viruses and genetic diseases.
Using DNA and RNA to treat cancers has been difficult because it is hard to get them to differentiate between cancerous and healthy cells.
This means a patient’s immune system can be adversely effected if healthy cells are attacked.
However, this was the first time scientists were able to develop a hairpin-shaped DNA strand that can activate a natural immune response to target and kill specific cancerous cells.
The findings were published in the Journal of the American Chemical Society.
We may have parted ways with our primate cousins millions of years ago, but a new study shows just how human beings continue to evolve in ways we never imagined.
Researchers from Biomedical Sciences Research Center “Alexander Fleming” (BSRC Flemming) in Greece and Trinity College Dublin, Ireland, have identified 155 genes in our genome that emerged from small, non-coding sections of DNA. Many appear to play a critical role in our biology, revealing how completely novel genes can rapidly evolve to become essential.
New genes typically arise through well known mechanisms like duplication events, where our genetic machinery accidently produces copies of pre-existing genes that can end up suiting new functions over time.
But the 155 microgenes pinpointed in this study seem to have appeared from scratch, in stretches of DNA that didn’t previously contain the instructions that our bodies use to build molecules.
Since the proteins these new genes are thought to encode would be incredibly tiny, these DNA sequences are hard to find and difficult to study, and therefore are often overlooked in research.
“This project started back in 2017 because I was interested in novel gene evolution and figuring out how these genes originate,” says evolutionary geneticist Nikolaos Vakirlis, from BSRC Flemming in Greece.
“It was put on ice for a few years, until another study got published that had some very interesting data, allowing us to get started on this work.”
That other study, published in 2020 by a team of researchers at the University of California San Francisco, catalogued a stack of microproteins that are produced by non-coding regions once described as ‘junk DNA’.
The team behind this new study subsequently created a genetic ancestral tree to compare those tiny sequences found in our genomes against those in 99 other vertebrate species, tracking the evolution of the genes over time.
Some of the new ‘microgenes’ identified in this new study can be tracked all the way back to the earliest days of mammals, while others are more recent additions. Two of the genes identified by the study seem to have emerged since the human-chimpanzee split, the researchers found.
“We sought to identify and examine cases in the human lineage of small proteins that evolved out of previously noncoding sequences and acquired function either immediately or shortly thereafter,” the team writes in their published paper.
“This is doubly important: for our understanding of the intriguing, and still largely mysterious phenomenon of de novo gene birth, but also for our appreciation of the full functional potential of the human genome.”
Microproteins are already known to have a diverse range of functions from helping to regulate the expressions of other genes to joining forces with larger proteins including our cell membranes. However, while some microproteins perform vital biological tasks, others are plain useless.
“When you start getting into these small sizes of DNA, they’re really on the edge of what is interpretable from a genome sequence, and they’re in that zone where it’s hard to know if it is biologically meaningful,” explains Trinity College Dublin geneticist Aoife McLysaght.
One gene with a role in constructing our heart tissue emerged when an ancestor common to humans and chimps branched off from the gorilla’s ancestry. If indeed this microgene emerged in the last few million years, it’s striking evidence that these evolving parts of our DNA can quickly become essential to the body.
The researchers then probed the sequences’ functions by deleting genes, one by one, in lab-grown cells. Forty-four of the cell cultures went on to show growth defects, confirming those now missing sections of DNA play critical roles in keeping us functioning.
In other comparative analyses, the researchers also identified in three of the new genes known variants associated with disease. The presence of these happenstance mutations at a single base position in the DNA may suggest some connection to muscular dystrophy, retinitis pigmentosa, and Alazami syndrome, but further research is going to be required to clarify these relationships.
In light of modern technology and medicine, appreciating the scale of biological change humans have experienced as a species at the hand of natural selection can be challenging. But our fitness has been shaped considerably by pressures of diet and disease over the millennia, and will undoubtedly continue to adapt even within a technologically advanced world.
Exactly how the spontaneous creation of new genes within the non-coding region happens is not yet clear, but with our newfound ability to track these genes, we may be closer to finding out.
“If we’re right in what we think we have here, there’s a lot more functionally relevant stuff hidden in the human genome,” says McLysaght.