Protein complex clears potential traffic jams in RNA production, finds research

Agencies
April 6, 2019

April 6: A new research has found that a protein complex plays a key role in clearing potential traffic jams in the production of RNA.

The research was published in the journal Genes & Development.

"The 'Ccr4-Not' complex is involved in nearly every step of this process from start to finish. Our new research shows that this complex has an additional function that helps maintain normal cellular function when something goes wrong during transcription," said Joseph C. Reese, a researcher.

During the transcription of RNA from DNA, RNAPII, itself a large complex made up of multiple protein subunits, travels along the strand of DNA reading the ATCG sequence and producing a complementary strand of RNA.

If the RNAPII encounters DNA damage, which can be caused by UV radiation and other sources, it can become stuck and prevent trailing polymerases from completing transcription of the gene, similar to how a stalled car prevents traffic behind it from flowing.

If this jam cannot be cleared, multiple RNAPIIs transcribing the same gene can start to pile up in a sort of traffic jam preventing the DNA from being repaired and hampering cell function.

"Defects in this pathway have been associated with a number of diseases and human syndromes, such as Cockayne syndrome- a neurodegenerative disorder that results in growth failure, neurological developmental defects, and sensitivity to UV light," Reese added.

RNA polymerase II (RNAPII), the enzyme that produces RNA from a DNA template, can become stuck due to damage to the DNA template, and these jams must be cleared to restore gene expression and normal cell function.

New research shows that the master regulatory complex, 'Ccr4-Not' performs this task, associating with RNAPII during the transcription of RNA from DNA and marking RNAPII for degradation when it becomes stuck, allowing the DNA to be repaired and normal cell function to resume.

"Normal cellular functions rely on what is sometimes called the 'central dogma of biology,'" said Reese.

The researchers used genetic methods and reconstitution biochemistry- a method whereby purified components of a cellular process can be added- taken away, and mixed in a precisely controlled manner to identify exactly how they function to show that 'Ccr4-Not' recruits factors that mark RNAPII with a small signalling molecule called ubiquitin.Attachment of ubiquitin to RNAPII triggers other cellular components to degrade the enzyme, clearing the jam.

"Mutating members of the 'Ccr4-Not' complex makes cells more sensitive to agents that damage the genome, but because 'Ccr4-Not' is involved in so many aspects of gene regulation it wasn't clear until now what its precise role was," said Reese.

"The fact that 'Ccr4-Not' recruited the destruction machinery to RNAPII was a surprising result, and suggests it acts as a tow truck to remove traffic jams throughout the genome," he added.

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Agencies
March 25,2020

The practice of washing your hands for 20 seconds is one of the best preventive measures you can take to avoid the spread of any virus including coronavirus as recommended by the WHO.

The modern day concept of handwashing was introduced by Hungaraian doctor Ignaz Semmelweis, in 19-th century Vienna. Semmelweis proposed the practice of washing hands with chlorinated lime solutions in 1847 while working in the city's general hospital.

Decades later, in the modern times too the practise has not lost it's relevance. To connect with savvy consumers the message is being sent through social media? But social media can also be a dark place where misinformation is rampant; consumers can end up being misguided and compromised on sensitive issues like health and hygiene.

Dettol, recently kickstarted its #HandWashChallenge on TikTok aiming to raise awareness on four simple steps of handwashing. Strategically aimed at creating awareness among audience, a unique song has been created pairing it extremely well with the hashtag #HandWashChallenge. The hashtag filter has a branded Dettol strip across the top with the hashtag and names the steps involved in washing hands. The user can dance out the steps to the challenge and share it with their friends to further amplify the message on hygiene and safety.

Commenting on the same, Pankaj Duhan, Chief Marketing Officer, RB Health South Asia said, "We are elated with the response to the #HandWashChallenge, it has definitely become one of the most successfully led initiatives by any of our brands at RB. Understanding the consumer's mindset is of the utmost importance to us, therefore our campaign communication is built in a way that creates meaningful conversations to drive awareness amongst consumers. The participation by TikTok users across India has helped deliver the right message in a more engaging and interactive manner.

"I personally would like to encourage more and more people to join this global health & hygiene educational exercise. Together, let us all build a healthier nation, four steps at a time."

He further said, "Over the past couple of weeks we have witnessed a lot of misinformation floating around hygiene practices, especially over the internet. Realizing the gravity of the issue and being the responsible brand, we felt it was our prerogative to initiate this awareness campaign."

The campaign witnessed several quirky activities on each day leading to increased consumer interest. Joining the force were some of Bollywood's popular celebrities like Kartik Aaryan and Urvashi Rautela among several other TikTok influencers who have millions of followers on the platform. As part of Phase II, Dettol plans to take the challenge global by encouraging more users to participate while the audience worldwide.

The challenge has witnessed over 18 Billion views and generated over 123K user participation videos in one week of starting the campaign.

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Agencies
July 3,2020

Apart from the many benefits of doing exercise, new research has now found that exercise can slow down or prevent the development of macular degeneration and may benefit other common causes of vision loss, such as glaucoma and diabetic retinopathy.

The new study from the University of Virginia School of Medicine found that exercise reduced the harmful overgrowth of blood vessels in the eyes of lab mice by up to 45 per cent. This tangle of blood vessels is a key contributor to macular degeneration and several other eye diseases.

The study represents the first experimental evidence showing that exercise can reduce the severity of macular degeneration, a leading cause of vision loss, the scientists report. Ten million Americans are estimated to have the condition.

"There has long been a question about whether maintaining a healthy lifestyle can delay or prevent the development of macular degeneration. The way that question has historically been answered has been by taking surveys of people, asking them what they are eating and how much exercise they are performing," said researcher Bradley Gelfand, PhD, of UVA's Center for Advanced Vision Science.

"That is basically the most sophisticated study that has been done. The problem with that is that people are notoriously bad self-reporters ... and that can lead to conclusions that may or not be true. This [study] offers hard evidence from the lab for the very first time," Gelfand added.

Enticingly, the research found that the bar for receiving the benefits from exercise was relatively low - more exercise didn't mean more benefit.

"Mice are kind of like people in that they will do a spectrum of exercise. As long as they had a wheel and ran on it, there was a benefit. The benefit that they obtained is saturated at low levels of exercise," Gelfand said.

An initial test comparing mice that voluntarily exercised versus those that did not found that exercise reduced the blood vessel overgrowth by 45%. A second test, to confirm the findings, found a reduction of 32 per cent.

The scientists aren't certain exactly how exercise is preventing the blood vessel overgrowth. There could be a variety of factors at play, they say, including increased blood flow to the eyes.

Gelfand, of UVA's Department of Ophthalmology and Department of Biomedical Engineering, noted that the onset of vision loss is often associated with a decrease in exercise.

"It is fairly well known that as people's eyes and vision deteriorate, their tendency to engage in physical activity also goes down. It can be a challenging thing to study with older people. ... How much of that is one causing the other?" he said.
The researchers already have submitted grant proposals in hopes of obtaining funding to pursue their findings further.

"The next step is to look at how and why this happens, and to see if we can develop a pill or method that will give you the benefits of exercise without having to exercise," Gelfand said.

He explained, "We're talking about a fairly elderly population [of people with macular degeneration], many of whom may not be capable of conducting the type of exercise regimen that may be required to see some kind of benefit." (He urged people to consult their doctors before beginning any aggressive exercise program.)
Gelfand, a self-described couch potato, disclosed a secret motivation for the research: "One reason I wanted to do this study was sort of selfish. I was hoping to find some reason not to exercise," he joked. "It turned out exercise really is good for you."

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Agencies
June 17,2020

Leading physicians are celebrating a small dose of good news that arrived Tuesday about dexamethasone, a cheap and widely used steroid shown to be able to save lives among COVID-19 patients, but also cautioning against releasing study results by press release during a global health emergency, like in the case of the latest dexamethasone study by University of Oxford.

"It will be great news if dexamethasone, a cheap steroid, really does cut deaths by one-third in ventilated patients with COVID19, but after all the retractions and walk backs, it is unacceptable to tout study results by press release without releasing the paper", Atul Gawande, surgeon and CEO of Haven Healthcare, tweeted.

"Bottom line is, good news," Dr. Fauci, America's foremost infectious diseases expert told a US newswire on Tuesday, soon after the dexamethasone results were announced in the UK.

Fauci, who has long championed the therapeutics-first view said that dexamethasone is a "significant improvement" in the available therapeutic options currently available.

On Medical Twitter and Facebook, doctors broadly agree that dexamethasone use aligns well with the way COVID19 attacks the body's immune system. Fauci said the results in the Oxford study make "perfect sense" in that context.

"We should see the number of people who actually survive go up, if the study holds up," virologist and epidemiologist Dr. Joseph Fair told a television network.

Global coronavirus cases crossed 8 million on Tuesday. In the US, Texas and Florida are facing a new wave of cases after lifting lockdown orders earlier than medical experts recommended. Amidst the relentless graph upwards, the dexamethasone study results injected hope for better survival rates among those most seriously ill.

World Health Organization chief scientist Soumya Swaminathan welcomed the results from the randomised control trial.

Dr Eugene Gu, Founder and CEO of CoolQuit tweeted that he is "genuinely impressed" with the UK dexamethasone trial. This may be a "game changer", he wrote.

"There's no conflict of interest as dexamethasone is a generic steroid. The mechanism of action makes sense because steroids can reduce cytokine storms and overactive immune systems that makes COVID-19 so deadly. The number needed to treat is 8 ventilated patients which is great."

The Oxford study found that dexamethasone reduced deaths by 35 percent in patients who needed treatment with breathing machines and by 20 percent in those only needing supplemental oxygen. Dexamethasone was one of 5 drugs studied in a large clinical trial in the United Kingdom named RECOVERY, short for Randomised Evaluation of COVID-19 Therapy.

Peter Horby, chief investigator of the University of Oxford clinical trial, said dexamethasone is the first drug to be shown to improve survival in COVID-19. Details of the study have not been released. The trial organisers said they made their announcement via a news release because of "the public health importance of these results." According to Horby's public comments, there was a lot of initial resistance to studying steroids.

During the study, 2,104 patients were randomly selected to be given 6 milligrams of dexamethasone once a day (either by mouth or by intravenous injection) for 10 days. That group was compared with 4,321 patients who received the usual care alone.

Researchers estimated that dexamethasone would prevent one death for every eight patients treated while on ventilators and one for every 25 patients on extra oxygen alone.

UK experts have called the study results a breakthrough in the fight against the virus. The researchers have promised they would publish the results soon.

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