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
April 21,2020

The Lockdown is not a cure but a critical strategy to prevent the geographical spread of COVID-19.

While pandemics at this level involves actual life threatening situations for individual's or significant others in one's immediate circle, it envisages a marked disruption in routine life. Even after the pandemic has been contained and will come to pass; it's aftermath will leave a trailblazer which demands planning and implementation of a post pandemic reconstruction of society with potentially traumatic experiences varying in intensity, multiplicity and duration.

Degree of Trauma

It would do well for each one of us to realise that the pandemic is "potentially traumatic", since not everyone will experience COVID -19 as a traumatic event in their lives. Yet, there will be those who may develop post pandemic stress reactions, depression and related dysfunction and pathological reactions while still other exhibit healthy reactions to the same set of circumstances.

"Psychological reactions to the pandemic can be distilled into four distinct prototypical patterns, namely, Resilience, Recovery, Chronic and Delayed patterns which may vary in intensity, multiplicity, and duration. Resilient individual have an ability to bounce back from adversity and experience modest or little disruption in normal functioning and are able to maintain a relatively stable, healthy levels of psychological functioning even after enduring the pandemic. Recovery pattern is characterised by relatively rapid reduction in symptoms and return to normal functioning whereas chronic pattern is characterised by symptoms and dysfunction of a long duration," says Pune-based military psychologist Lt Col Dr Samir Rawat.

Challenges at the Individual and Community Levels

From a psychological perspective, post pandemic reconstruction would entail catering to the problems, concerns and needs of those adversely impacted by the COVID -19 with stress symptoms typically characterised by individual's experiencing an overwhelming trauma of the pandemic (for example, recurring nightmares/ breaking into a cold sweat, flashback of stressful events, increasing irritability, low frustration tolerance or emotional numbing).

It could also manifest in depressive symptoms which may result in lack of interest or diminished pleasure in activities and things which you earlier liked to do, feelings of worthlessness or even survivor guilt in case of a loss of a loved one due to COVID-19, fleeting thoughts of death and suicidal ideation. Physical symptoms, on the other hand could be a decrease in appetite, weight and sleep problems, inability to focus and lack of concentration.

Undoubtedly, the pandemic will cause a financial loss of varying magnitude to many, especially the marginalised and economically disadvantaged strata of daily wage earners; it will also lead to loss of jobs (already beginning to show), homelessness, occupational difficulties and new challenges in interpersonal relations at work and on the home front, besides physical health problems and psychological barriers with new norms of accepted social behaviour (social distancing, handshakes, an obsession for cleanliness to name a few).

Emotional battles

Many factors may influence whether individuals come out stronger and more resilient or surrender to the pandemic. Emotion Regulation is one such long term critical factor that can play an important role in contributing to varying degrees of adaptation with negative or positive outcomes. While we know that primary emotions are fear, anger, disgust, joy, anticipation, acceptance, sadness and surprise, other basic emotions include wonder, love, desire, joy, hatred, sadness, attachment, disgust, rage and even expectancy .

To be able to regulate these emotions and avoid negativity , especially on social media platforms is likely to increase efforts in emotion regulation which involves initiating, increasing or maintaining an emotional response.

This means by regulating or on the other hand by stopping, decreasing or avoiding an emotional response, that is, by down-regulating, depending on the individual's objectives and goals or his /her ability to regulate emotions in the valued and given direction.

"One of the best ways to regulate emotions is through cognitive restructuring wherein we change the way we think; after all it is not the event but the interpretation of the event which is perceived as stressful and finding meaning promotes resilience and reduces risk and vulnerability to stress," advises Dr Rawat.

Adding, "Clearly, we need to have a psychological plan to prevent, mitigate and minimise negative outcomes by post pandemic reconstruction of society at an individual and community level all over the country; this has to be integrated by all leaders across verticals in diverse domains."

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Agencies
May 30,2020

Drinking coffee may help reduce the risk of certain digestive disorders, including gallstone disease and pancreatitis, a new study has suggested.

The study from the Institute for Scientific Information on Coffee (ISIC) also highlighted other beneficial effects that coffee consumption may have on the process of digestion, including supporting gut microflora and promoting gut motility.

"Data indicates benefits against common digestive complaints such as constipation, as well as a potential reduction in the risk of more serious conditions like chronic liver diseases," said study author Carlo La Vecchia from the University of Milan in Italy.

Gallstone disease is a common digestive disorder, caused by the accumulation of gallstones in the gallbladder or bile duct, which affects approximately 10-15 per cent of the adult population.

While the mechanism by which coffee may protect against gallstone disease is not yet known, it has been observed that the risk for the condition declines with increasing daily consumption of coffee, the researchers said.

Caffeine is thought to play a role in these associations, as the same effect is not observed with decaffeinated coffee.

A common question among consumers and focus area for research is whether coffee is associated with heartburn or gastro-oesophageal reflux disease (GORD).

While a small number of studies have suggested an association between coffee drinking and GORD, the majority of studies reviewed suggest that coffee is not a major trigger of these conditions.

The report also reviewed a growing area of health and nutrition research, namely: the effect of coffee on the gut microflora (microorganism populations).

Recent studies suggest that populations of the beneficial gut bacteria Bifidobacterium spp, increase after drinking coffee.

The findings showed the dietary fibre and polyphenols found in coffee, support the healthy growth of microflora populations.

Additional research findings highlighted that coffee consumption is thought to stimulate digestion by encouraging the release of gastric acid, bile and pancreatic secretions.

Coffee is one of the most widely researched components of the diet, and its effect on digestion remains a growing area of research, the researchers noted.

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Agencies
June 22,2020

A team of scientists has produced first open source all-atom models of full-length COVID-19 Spike protein that facilitates viral entry into host cells – a discovery that can facilitate a faster vaccine and antiviral drug development.

The group from Seoul National University in South Korea, University of Cambridge in the UK and Lehigh University in the US produced the first open-source all-atom models of a full-length S protein.

The researchers say this is of particular importance because the S protein plays a central role in viral entry into cells, making it a main target for vaccine and antiviral drug development.

"Our models are the first full-length SARS-CoV-2 spike (S) protein models that are available to other scientists," said Wonpil Im, a professor in Lehigh University.

"Our team spent days and nights to build these models very carefully from the known cryo-EM structure portions. Modeling was very challenging because there were many regions where simple modeling failed to provide high-quality models," he wrote in a paper published in The Journal of Physical Chemistry B.

Scientists can use the models to conduct innovative and novel simulation research for the prevention and treatment of Covid-19.

Though the coronavirus uses many different proteins to replicate and invade cells, the Spike protein is the major surface protein that it uses to bind to a receptor.

The total number of global COVID-19 cases was nearing 9 million, while the deaths have increased to over 467,000, according to the Johns Hopkins University.

With 2,279,306 cases and 119,967 deaths, the US continues with the world's highest number of COVID-19 infections and fatalities, according to the CSSE.

Brazil comes in the second place with 1,083,341 infections and 50,591 deaths.

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