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 27,2020

New Delhi, Mar 27: The Centre has restricted sale and distribution of "hydroxychloroquine" declaring it as an essential drug to treat the COVID-19 patients and meet the requirements of emergency arising due to the pandemic.

The Ministry of Health and Family Welfare on Thursday made the announcement making it clear that the order "shall come into force on the date of its publication in the official Gazette".

In the order, the government declared that the Central government is "satisfied that the drug hydroxychloroquine is essential to meet the requirements of emergency arising due to pandemic COVID-19 and in the public interest, it is necessary and expedient to regulate and restrict the sale and distribution of the drug 'hydroxychloroquine' and preparation based thereon for preventing their misuse".

"Now, therefore, in exercise of the powers conferred by Section 26B of the Drugs and Cosmetics Act, 1940 (23 of 1940), the Central government hereby directs that sale by retail of any preparation containing the drug Hydroxychloroquine shall be in accordance with the conditions for sale of drugs specified in Schedule H1 to the Drugs and Cosmetics Rules, 1945."

The order came at a time when the novel coronavirus claimed 16 lives and infected over 600 people across India.

The announcement regarding ban of sale and distribution of the drug was made by the government earlier but it issued an official Gazette notification on Thursday signalling that hydroxychloroquine -- an anti-Malaria drug -- will work as a medicine for treating coronavirus infected patients as well.

Recently, the national task force for COVID-19 constituted by Indian Council for Medical Research (ICMR) has recommended hydroxy-chloroquine as a preventive medication.

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Agencies
May 18,2020

China, where the novel coronavirus originated, has reported 111 cases since beginning of May, which shows the infection rate has dipped, and 3 deaths since April 27, according to the WHO. A Shanghai-based Noida doctor says China is close to winning the battle against COVID-19, and the combination of zinc, hydroxychloroquine (HCQ) and antibiotic azithromycin has been able to save the lives of coronavirus patients.

Speaking to media persons, Dr Sanjeev Choubey, Medical Director Internal Medicine at St. Michael Hospital said this combination has been adopted as a line of treatment for patients infected with coronavirus, and as a result patients are recovering, decreasing their need for intensive care.

What is the line of treatment for COVID-19 patients, which also include asymptomatic patients?

The combination of zinc, hydroxychloroquine and antibiotic azithromycin has produced positive results, and it helped in the recovery of many COVID-19 patients. The combination -- Ascorbic Acid, B-complex, Zinc, Selenium, L-carnitine, Vitamin B-12 and Glutathione normal saline should be administered on patients twice a week for at least 6 weeks. This is COVID-19 treatment protocol for prophylaxis, and it implies both asymptomatic and symptomatic along with other medicine support.

Based on your experience on COVID-19 in China, after how many tests, is it safe to call a person coronavirus free?

The coronavirus should be performed at least 9 times, before terming a patient COVID-19 free. It is a standard in China. This procedure has worked in China and it will also work in India. Minimum five tests should be mandatory through RT-PCR.

Does coronavirus majorly attack the respiratory system or it could lead to organ failure too?

Line of treatment should not be just looking at the respiratory system, as the problem lies somewhere else. COVID-19 attacks many vital organs in the body. In China, a coronavirus patient died from a stroke. In the autopsy it was found that the innermost layer in the arteries was swollen. It was concluded that coronavirus had inflamed the layer of the arteries leading to clotting, which was a factor in generating a heart attack. Therefore, COVID-19 is not just a respiratory problem.

Amid the coronavirus pandemic, should autopsy be made mandatory in the case of unpredictable death or where reasons for death are not unknown?

Patients below 50 years, who die suddenly and the reasons are not known, then it should be mandatory to conduct the autopsy. After death, coronavirus is active in the body for five days, and it fades away on day 6. Therefore, if an autopsy is done then it will help in understanding this disease. In China, we have seen young COVID-19 patients, aged 22 and 28, succumbed to strokes.

Since the beginning of May, India has recorded more than 2,000 cases everyday in the first week, then it jumped past 3,000 mark in the second week. Finally, the tally is 4,987 on May 17. At 90,927 cases, has India progressed into community transmission or Stage3?

Yes, India has moved into Stage 3. The data suggests that 3,000 to 4,000 active COVID-19 cases, who are asymptomatic, are moving around and spreading the infection. The research has indicated that COVID-19 from an infected person spreads in 30 minutes to non-infected persons. The relaxation on the lockdown will certainly contribute to a high infection rate.

Do you think India has reached its peak in COVID-19 cases, or the sharp rise will continue till July end?

It seems India has already reached its peak and cases will begin to come down from June end or beginning of July first week. If social distancing norms are followed then certainly things can improve, but if not followed then it may get worse. High population density is a major contributor for the increase in cases. The government should continue to focus on finding hotspots, and urge people to follow the rules, eventually it is for people’s own benefit.

Has China won the battle against COVID-19?

It seems China has won the battle by not opening up Wuhan. The Chinese are following a COVID-19 patient’s engagement program, where the authorities continuously interact with people infected with the disease. The Government of India should reward people who follow the guidelines; it will help in setting up a positive trend in the society.

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Agencies
May 6,2020

Washington D.C., May 5: Working from home has become the new normal ever since the outbreak of coronavirus and in today's time the work duties can be easily dealt with by means of mobile devices at home.

However, this easy use of technology, mobile devices for that matter, has the potential to blur the fine line between work and the other daily life routines.

But, contrary to the belief, a study at the University of Jyvaskyla reveals that the mixing of work and other daily life routines may have more benefits than previously assumed, and points to the importance of boundary-spanning communication.

A smartphone enables phone calls, email, and file transfers from the comfort of home. The study shows that there may be more effective ways to maximise the benefits of smartphone use, without diminishing employees' flexibility and the use of these technologies.

"People often forget to talk about positive effects, such as autonomy and freedom the employees gain when they have the flexibility to schedule their work," said Postdoctoral Researcher Ward van Zoonen from JYU, who with his colleagues examined the use of smartphones for work matters outside working hours.

The study paid special attention to the benefits of talking about domestic matters with the immediate supervisor outside the working hours given to an employee.

"This reduces the conflict between work and other life," van Zoonen said.

"If people in an organisation strive for more dialogue between employees' different life domains, it is possible to create a functional environment where people can talk about different matters."

The research findings show that when employees communicate across boundaries and talk at work about their life in other respects, they can receive new kinds of support and understanding from their immediate supervisor.

"This kind of communication creates a low threshold for contacting one's supervisor, which helps employees build a balance between the different domains of their lives and strengthens their organisational identification," said Professor Anu Sivunen describing the findings.

This means that tight working time restrictions to protect employees might not be beneficial after all, if they hinder reaching the positive results indicated in this research.

For the study, a survey was taken of 367 employees who were asked questions such as -- how much they talk about their work with their family, and how much they talk about their family with their immediate supervisor.

"Both supervisors and their employees answered the surveys, and the study actually focused on their mutual communication," Sivunen said.

"Usually people at workplaces are interested in how communication within the work community is succeeding. It is often forgotten how an immediate supervisor can take an employer's other life into account and thereby help the employee gain work-related benefits."

"Communication with one's immediate supervisor during flexible working hours, also on matters other than work, could ease the daily lives of many employees if they could share the possible challenges of their family life or free time with their supervisor in these settings," Sivunen added.

According to the study, such a practice could make the supervisor aware of the employee's situation as he/she works from home and the related impacts on their work performances.

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