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
June 27,2020

After admitting that the world may have a COVID-19 vaccine within one year or even a few months earlier, the World Health Organisation (WHO) on Friday said that UK-based AstraZeneca is leading the vaccine race while US-based pharmaceutical major Moderna is not far behind.

WHO Chief Scientist Soumya Swaminathan stated that the AstraZeneca's coronavirus vaccine candidate is the most advanced vaccine currently in terms of development.

"I think AstraZeneca certainly has a more global scope at the moment in terms of where they are doing and planning their vaccine trials," she told the media.

AstraZeneca's Covid-19 vaccine candidate developed by researchers from the Oxford University will likely provide protection against the disease for one year, the British drug maker's CEO told Belgian radio station Bel RTL this month.

The Oxford University last month announced the start of a Phase II/III UK trial of the vaccine, named AZD1222 (formerly known as ChAdOx1 nCoV-19), in about 10,000 adult volunteers. Other late-stage trials are due to begin in a number of countries.

Last week, Swaminathan had said that nearly 2 billion doses of the COVID-19 vaccine would be ready by the end of next year.

Addressing the media from Geneva, she said that "at the moment, we do not have a proven vaccine but if we are lucky, there will be one or two successful candidates before the end of this year" and 2 billion doses by the end of next year.

Scientists predict that the world may have a COVID-19 vaccine within one year or even a few months earlier, said the Director-General of the World Health Organization even as he underlined the importance of global cooperation to develop, manufacture and distribute the vaccines.

However, making the vaccine available and distributing it to all will be a challenge and will require political will, WHO chief Tedros Adhanom Ghebreyesus said on Thursday during a meeting with the European Parliament's Committee for Environment, Public Health and Food Safety.

One option would be to give the vaccine only to those who are most vulnerable to the virus.

There are currently over 100 COVID-19 vaccine candidates in various stages of development.

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News Network
June 20,2020

Washington, Jun 20: Pregnant and postpartum women are usually at a high risk of depression and anxiety - one in seven women struggle with symptoms in the perinatal period and the coronavirus pandemic is exacerbating those struggles according to a recent study.

The study was published in Frontiers in Global Women's Health, which found that the likelihood of maternal depression and anxiety has substantially increased during the health crisis.

"The social and physical isolation measures that are critically needed to reduce the spread of the virus are taking a toll on the physical and mental health of many of us," said Dr. Margie Davenport of the University of Alberta, Canada, who co-authored the study.

For new moms, those stresses come with side effects.

"We know that experiencing depression and anxiety during pregnancy and the postpartum period can have detrimental effects on the mental and physical health of both mother and baby that can persist for years," said Davenport.

Such effects can include premature delivery, reduced mother-infant bonding, and developmental delays in infants.

The study surveyed 900 women - 520 of whom were pregnant and 380 of whom had given birth in the past year - and asked about their depression and anxiety symptoms before and during the pandemic.

Before the pandemic began, 29 percent of those women experienced moderate to high anxiety symptoms, and 15 percent experienced depressive symptoms. During the pandemic, those numbers increased - 72 percent experienced anxiety and 41percent experienced depression.

Because lockdown measures have affected daily routines and access to gyms, researchers also asked women whether their exercise habits had changed. Of the women surveyed, 64 percent reduced their physical activity since the pandemic began, while 15 percent increased and 21 percent experienced no change.

Exercise is a known way to ease depression symptoms, so limited physical activity may result in an uptick in depressive symptoms. Indeed, the study found that women who engaged in at least 150 minutes of moderate physical activity a week had significantly lower symptoms of depression and anxiety.

The findings are somewhat limited given the fact that researchers could not survey women before the pandemic began (since they could not know a pandemic would occur). The women surveyed could only offer their pre-pandemic symptoms in hindsight.

Also, while the researchers asked women about their symptoms using validated measures, only mental health care professionals can validly diagnose an individual with depression or anxiety.

The study was specifically interested in the impact of COVID-19 on new moms, but Davenport says maternal mental health is a critical issue no matter the time.

"Even when we are not in a global pandemic, many pregnant and postpartum women frequently feel isolated whether due to being hospitalized, not having family or friends around or other reasons," she said.

"It is critical to increase awareness of the impact of social (and physical) isolation on the mental health of pregnant and postpartum women," Davenport added.

Increased awareness makes diagnosis and treatment - the ultimate goal - more likely.

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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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