Gene-editing damages DNA more than thought: study

Agencies
July 17, 2018

Paris, Jul 17:  A revolutionary gene editing technique hailed as the future of disease eradication and mooted for a Nobel Prize may be less precise and cause more cell damage than previously thought, researchers said Monday.

Lab experiments using mouse and human cells revealed that the CRISPR-Cas9 technique "frequently" caused "extensive" gene mutations, a study team reported.

"This is the first systematic assessment of unexpected events resulting from CRISPR-Cas9 editing," said Allan Bradley of the Wellcome Sanger Institute in England, where the team conducts research.

The research showed that "changes in the DNA have been seriously underestimated before now," said Bradley, who co-authored a study published in the journal Nature Biotechnology.

The mutations have not been shown to be harmful, nor benign.

"It is important that anyone thinking of using this technology for gene therapy proceeds with caution and looks very carefully to check for harmful effects," Bradley said in a statement issued by the institute.

First unveiled about six years ago, CRISPR-Cas9 allows scientists to insert, remove and correct a faulty sequence on a strand of DNA in a cell with pinpoint precision.

It has raised hopes that one-day disease-causing genes could be removed or altered before a baby is even born.

In recent years, CRISPR-Cas9 has repeatedly been predicted to win the Nobel Chemistry Prize.

CRISPRs -- clustered regularly interspaced short palindromic repeats -- are part of the immune defence system in bacteria, used to hone in on the exact spot on the genome where the cut should be made.

Cas9 is a protein used as "scissors" to snip through the faulty gene, which is then replaced or fixed by the cell's own DNA repair mechanism.

The technique's safety has not yet been proven, and it is not approved for use in human therapy.

So far, researchers have used it to improve hearing in mice going deaf and to fix a disease-causing mutation in cloned, early-stage human embryos.

But the new finding raises "safety implications," the team said.

They found "large genetic rearrangements such as DNA deletions and insertions" in cells, which could lead to important genes being switched on or off and causing dangerous changes.

The research also showed that standardized tests do not pick up damage to DNA caused by CRISPR-Cas9.

Experts not involved in the study said it was unclear how such large, unintended changes were not noticed before.

But, "the results give no reason to panic or to lose faith in the methods when they are carried out by those who know what they are doing," said Robin Lovell-Badge of The Francis Crick Institute, a biomedical research centre in London.

For Francesca Forzano, a consultant in clinical genetics and genomics with the Guy's and St Thomas' NHS Foundation Trust, the work showed that CRISPR-Cas9 "is much less safe than previously thought" and that safety-monitoring techniques were "not entirely adequate".

More research is needed before any clinical application of the method is considered, said Forzano.

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Agencies
May 10,2020

Washington D.C., May 9: Do the middle age feel much stressful now, and seems to have changed over time, if compared to the life in the 90s? Well, this recent study indicates that it might be true.

The study has signalled to the fact that life may become more stressful majorly for middle-aged people than it was in the 1990s. The researchers reached this analysis even before the novel coronavirus started sweeping the globe.

A team of researchers led by Penn State found that across all ages, there was a slight increase in daily stress in the 2010s compared to the 1990s. But when researchers restricted the sample to people between the ages of 45 and 64, there was a sharp increase in daily stress.

"On average, people reported about 2 percent more stressors in the 2010s compared to people in the past," said David M. Almeida, professor of human development and family studies at Penn State.

"That's around an additional week of stress a year. But what really surprised us is that people at mid-life reported a lot more stressors, about 19 percent more stress in 2010 than in 1990. And that translates to 64 more days of stress a year."

Almeida said the findings were part of a larger project aiming to discover whether health during the middle of Americans' lives has been changing over time.

"Certainly, when you talk to people, they seem to think that daily life is more hectic and less certain these days," Almeida said.

For the study, the researchers collected data from 1,499 adults in 1995 and 782 different adults in 2012.

Almeida said the goal was to study two cohorts of people who were the same age at the time the data was collected but born in different decades. All study participants were interviewed daily for eight consecutive days.

During each daily interview, the researchers asked the participants about their stressful experiences throughout the previous 24 hours.

They asked questions related to arguments with family or friends or feeling overwhelmed at home or work, so and so. The participants were also asked how severe their stress was and whether those stressors were likely to impact other areas of their lives.

"We were able to estimate not only how frequently people experienced stress, but also what those stressors mean to them," Almeida said.

"For example, did this stress affect their finances or their plans for the future. And by having these two cohorts of people, we were able to compare daily stress processes in 1990 with daily stress processes in 2010," Almeida added.

After analyzing the data, the researchers found that participants reported significantly more daily stress and lower well-being in the 2010s compared to the 1990s.

Additionally, participants reported a 27 percent increase in the belief that stress would affect their finances and a 17 percent increase in the belief that stress would affect their future plans.

Almeida said he was surprised not that people were more stressed now than in the 90s, but at the age group that was mainly affected.

"We thought that with economic uncertainty, life might be more stressful for younger adults. But we didn't see that. We saw more stress for people at mid-life," Almeida said.

"And maybe that's because they have children who are facing an uncertain job market while also responsible for their own parents. So it's this generational squeeze that's making stress more prevalent for people at mid-life," he concluded.

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Agencies
January 26,2020

High-protein diets may help people lose weight and build muscle, but there is a downside to it --a greater heart attack risk. Researchers now report that high-protein diets boost artery-clogging plaque.

The research in mice showed that high-protein diets spur unstable plaque -- the kind most prone to rupturing and causing blocked arteries.

More plaque buildup in the arteries, particularly if it's unstable, increases the risk of heart attack.

"There are clear weight-loss benefits to high-protein diets, which has boosted their popularity in recent years," said senior author Babak Razani, associate professor at Washington University School of Medicine in St. Louis, Missouri.

"But animal studies and some large epidemiological studies in people have linked high dietary protein to cardiovascular problems. We decided to take a look at whether there is truly a causal link between high dietary protein and poorer cardiovascular health," Razani added.

The researchers studied mice who were fed a high-fat diet to deliberately induce atherosclerosis, or plaque buildup in the arteries.

Some of the mice received a high-fat diet that was also high in protein. And others were fed a high-fat, low-protein diet for comparison.

The mice on the high-fat, high-protein diet developed worse atherosclerosis -- about 30 per cent more plaque in the arteries -- than mice on the high-fat, normal-protein diet, despite the fact that the mice eating more protein did not gain weight, unlike the mice on the high-fat, normal-protein diet.

"A couple of a scoop of protein powder in a milkshake or smoothie adds something like 40 grams of protein -- almost equivalent to the daily recommended intake," Razani said.

"To see if protein has an effect on cardiovascular health, we tripled the amount of protein that the mice receive in the high-fat, high-protein diet -- keeping the fat constant. Protein went from 15 per cent to 46 per cent of calories for these mice".

Plaque contains a mix of fat, cholesterol, calcium deposits and dead cells. Past work by Razani's team and other groups has shown that immune cells called macrophages work to clean up plaque in the arteries.

But the environment inside plaque can overwhelm these cells, and when such cells die, they make the problem worse, contributing to plaque buildup and increasing plaque complexity.

"In mice on the high-protein diet, their plaques were a macrophage graveyard," Razani informed.

To understand how high dietary protein might increase plaque complexity, Razani and his colleagues also studied the path protein takes after it has been digested -- broken down into its original building blocks, called amino acids.

"This study is not the first to show a telltale increase in plaque with high-protein diets, but it offers a deeper understanding of the impact of high protein with the detailed analysis of the plaques," said Razani.

"This work not only defines the critical processes underlying the cardiovascular risks of dietary protein but also lays the groundwork for targeting these pathways in treating heart disease," he added.

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News Network
February 22,2020

Feb 22: The subjective feeling of well-being experienced by many people with the practice of meditation is associated with specific changes in the brain, according to a study which may lead to better clinical recommendations of the practice.

The study, published in the journal Brain and Cognition, examined the effects of the technique known as Transcendental Meditation (TM), which consists of the silent repetition of a meaningless sound.

In the study, the researchers from the IMT School for Advanced Studies Lucca in Italy, enrolled 34 healthy young volunteers and divided them in two groups.

They said the first group practised TM 40 minutes per day in two sessions of 20 minutes each, one in the morning and the other in the evening.

The second group, the scientists said, did not change its daily routine.

Using questionnaires, they also measured the anxiety and stress levels of all the participants at the beginning of the study, as well as the subjects' ability to manage stressful situations.

According to the researchers, the participants were also subjected to a functional magnetic resonance imaging (fMRI) brain scan, in order to measure the organ's activity at rest, and changes in the excitation among different cerebral areas.

They repeated the tests after three months, at the end of the study.

According to the study, the levels of anxiety and stress perceived by the subjects who followed the meditation program were significantly reduced in comparison with those of the volunteers who did not practice TM.

"Magnetic resonance imaging also shows that the reduction of anxiety levels is associated with specific changes in the connectivity between different cerebral areas, such as precuneus, left parietal lobe and insula, which all have an important role in the modulation of emotions and inner states," said study co-author Giulia Avvenuti from the IMT School for Advanced Studies Lucca.

"In the control group, instead, none of these changes was observed. The fact that Transcendental Meditation has measurable effects on the 'dialogue' between brain structures involved in the modulation of affective states opens new perspectives for the understanding of brain-mind relationships," said Pietro Pietrini, IMT School's Director, and co-author of the study.

"It also extends the results of recent research suggesting that drugs therapies and psychotherapy leverage on the same biological mechanism," Pietrini said.

According to the researchers, even a few months of practice of TM can have positive effects which can be correlated with measurable changes in the brain.

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