Scientists discover mechanism that may prevent death of cells

July 21, 2017

London, Jul 19: Scientists in the UK have discovered a new mechanism that could help slow down the progression of neurodegenerative diseases like dementia and neurological decline associated with ageing, according to a research published today.Scientists

The UK's University of Sheffield scientists identified that tuning up the activity pathway of the DNA's natural repair toolkit – which normally helps to restore breakages in genetic material - could help to prevent the death of nerve cells which trigger neurological diseases.

The scientists examined the C9 or f72 gene which contains six DNA nucleotides – the building blocks of DNA where all important cellular information is stored.

When this series of nucleotides is expanded and repeated multiple times, neurodegenerative diseases can occur. The expansions of the gene forms genetic material called 'R-loops' which make the DNA vulnerable to breakages.

They found that accumulation of R-loops and increased DNA breakage in neurons lead to neurodegenerative diseases.

Human cells have their own repair toolkits specially designed to fix breaks in DNA, however, the products of the expansion over-activate a process called autophagy – a process that gets rid of misfolded or "unwanted" proteins.

The new study, jointly directed by Professor Sherif El- Khamisy and Professor Mimoun Azzouz, published in Nature Neuroscience, shows that the expansion driven over-activation of this process can degrade some of the very precious DNA toolkits, meaning the cells will eventually die.

"We were able to shut down the out-of-control degradation process, which runs down the cell's ability to fix genomic breaks, using genetic techniques. Even though the DNA was still damaged, the cells were able to cope and did not die" said El-Khamisy.

Discovering this new mechanism and its consequence is a significant step towards developing new therapies for motor neurone disease and other neurodegenerative conditions, El- Khamisy said.

The discovery based on work conducted in cellular and mouse models of the disease could pave the way for new therapies for devastating diseases such as Motor Neurone Disease (MND), which is one of the most common neurodegenerative disorders affecting younger people in the middle of their active life.

There are currently no treatments to tackle the disease. "This discovery is addressing one of the major challenges of namely the poor understanding of how neurones die in these MND patients," Azzouz said.

"The research paves the way for an exciting horizon to accelerate the pace of therapeutic development for MND. Our aim now is to identify targets that can preserve the DNA toolkits and rescue neurons from degeneration," Azzouz said.

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Agencies
July 6,2020

The Covid-19 pandemic has made an unprecedented impact on the Indian businesses, particularly small and medium enterprises (SMEs) and startups. According to a joint survey by FICCI and Indian Angel Network (IAN), the pandemic has hit the businesses of around 70% startups.

With uncertainty in the business environment and an unexpected shift in priorities of the government as well as corporates, many startups are struggling to survive, it says.

In a nationwide survey on the 'Impact of Covid-19 on Indian Startups' involving 250 startups, 70% participants said their businesses had been impacted by Covid-19 and around 12% had shut operations.

The survey shows only 22% startups have cash reserves to meet the fixed cost expenses over the next 3-6 months, and 68% are reducing operational and administrative expenses.

Around 30% of the companies said they would retrench employees if the lockdown was extended too long. The 43% startups have already started 20-40% salary cuts over April-June.

Over 33% startups said investors had put the investment decision on hold and 10% said the deals had been scrapped. Only 8% startups had received funds as per the deals signed before Covid-19 outbreak, the survey revealed.

The reduced funding has forced startups to put a hold on business development and manufacturing activities, which has resulted in loss of projected orders.

The survey highlights the need of an urgent relief package for startups, including possible purchase orders from the government, tax relief and swifter tax refunds, and immediate fiscal support measures, including grants, soft loans and payroll grants.

Besides 250 startups, 61 incubators and investors also participated in the survey.

While 96% of investors accepted that their investments in startups had been impacted by Covid-19, 92% said their investments in startups would continue to be low over the next six months.

Around 59% investors said they would prefer to work with the existing portfolio firms in the coming months. Only 41% said they would consider new deals.

"A comparison of priority investment sectors before and during Covid-19 shows 35% investors are now looking at investments in healthcare startups, followed by EdTech, AI/Deep Tech, FinTech and Agri," said the survey.

Around 44% incubators surveyed said their day-to-day operations had been considerably hit by Covid-19. Most incubators are now supporting their portfolio firms by providing them virtual platforms to interact with mentors, investors and industries.

Dilip Chenoy, FICCI Secretary General, said, "The startup sector is stressed for survival at the moment. The investment sentiment is also subdued and is expected to remain so in the coming months. Lack of working capital and cash flows may lead to major layoffs over the next 3-6 months."

Indian startups needed an enabling ecosystem and flow of funds to continue operations, the survey said.

Padmaja Ruparel, President, Indian Angel Network & Co-Chair of FICCI Startup Committee, said, "In these uncertain times, as investors, we must play an important role to provide the Indian startups funding, mentoring and hand-holding support to stay afloat and come out at the other end of this crisis."

To that end, IAN recently announced a debt fund to help IAN portfolio companies raise working capital and ensure business continuity by partnering with debt providers.

This must be replicated on a wider scale, so a larger number of startups are provided the capital support to make it during these tough times, Ruparel said.

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Agencies
July 11,2020

Citing the current dismal aviation scenario, Air India is terminating the services of trainee cabin crew and cabin crew by withdrawing the offer of employment of those who were under training.

As per sources, the new crew and trainee pilots might reduce contracts from five years to one year. Sources said Air India is terminating 1,200 crew and employees who are more than 55-yr-old including 190 trainee pilots.

In a letter reviewed by IANS, Air India has informed an applicant who had been selected as cabin crew in August 2019 subject to successful completion of training.

"On behalf of Air India we would like to thank you for the interest shown by you in joining our organization. However, in view of the current aviation scenario, it would not be possible for Air India to impart any further training to you for engaging your services," the company said.

"In view of the above reasons, which are beyond the control of the company, it has been decided to discontinue your training arrangements and dispense with the offer of engagement with immediate effect. The bank guarantee furnished by you at the time of joining is returned herewith," Air India told the cabin crew.

"Once again on behalf of Air India we thank you for your cooperation and trust that you will appreciate the circumstances under which we are constrained to discontinue the training arrangements," the carrier said.

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News Network
April 17,2020

Paris, Apr 17: Even as virologists zero in on the virus that causes COVID-19, a very basic question remains unanswered: do those who recover from the disease have immunity?

There is no clear answer to this question, experts say, even if many have assumed that contracting the potentially deadly disease confers immunity, at least for a while.

"Being immunised means that you have developed an immune response against a virus such that you can repulse it," explained Eric Vivier, a professor of immunology in the public hospital system in Marseilles.

"Our immune systems remember, which normally prevents you from being infected by the same virus later on."

For some viral diseases such a measles, overcoming the sickness confers immunity for life.

But for RNA-based viruses such as Sars-Cov-2 -- the scientific name for the bug that causes the COVID-19 disease -- it takes about three weeks to build up a sufficient quantity of antibodies, and even then they may provide protection for only a few months, Vivier told AFP.

At least that is the theory. In reality, the new coronavirus has thrown up one surprise after another, to the point where virologists and epidemiologists are sure of very little.

"We do not have the answers to that -- it's an unknown," Michael Ryan, executive director of the World Health Organization's Emergencies Programme said in a press conference this week when asked how long a recovered COVID-19 patient would have immunity.

"We would expect that to be a reasonable period of protection, but it is very difficult to say with a new virus -- we can only extrapolate from other coronaviruses, and even that data is quite limited."

For SARS, which killed about 800 people across the world in 2002 and 2003, recovered patients remained protected "for about three years, on average," Francois Balloux director of the Genetics Institute at University College London, said.

"One can certainly get reinfected, but after how much time? We'll only know retroactively."

A recent study from China that has not gone through peer review reported on rhesus monkeys that recovered from Sars-Cov-2 and did not get reinfected when exposed once again to the virus.

"But that doesn't really reveal anything," said Pasteur Institute researcher Frederic Tangy, noting that the experiment unfolded over only a month.

Indeed,several cases from South Korea -- one of the first countries hit by the new coronavirus -- found that patients who recovered from COVID-19 later tested positive for the virus.

But there are several ways to explain that outcome, scientists cautioned.

While it is not impossible that these individuals became infected a second time, there is little evidence this is what happened.

More likely, said Balloux, is that the virus never completely disappeared in the first place and remains -- dormant and asymptomatic -- as a "chronic infection", like herpes.

As tests for live virus and antibodies have not yet been perfected, it is also possible that these patients at some point tested "false negative" when in fact they had not rid themselves of the pathogen.

"That suggests that people remain infected for a long time -- several weeks," Balloux added. "That is not ideal."

Another pre-publication study that looked at 175 recovered patients in Shanghai showed different concentrations of protective antibodies 10 to 15 days after the onset of symptoms.

"But whether that antibody response actually means immunity is a separate question," commented Maria Van Kerhove, Technical Lead of the WHO Emergencies Programme.

"That's something we really need to better understand -- what does that antibody response look like in terms of immunity."

Indeed, a host of questions remain.

"We are at the stage of asking whether someone who has overcome COVID-19 is really that protected," said Jean-Francois Delfraissy, president of France's official science advisory board.

For Tangy, an even grimmer reality cannot be excluded.

"It is possible that the antibodies that someone develops against the virus could actually increase the risk of the disease becoming worse," he said, noting that the most serious symptoms come later, after the patient had formed antibodies.

For the moment, it is also unclear whose antibodies are more potent in beating back the disease: someone who nearly died, or someone with only light symptoms or even no symptoms at all. And does age make a difference?

Faced with all these uncertainties, some experts have doubts about the wisdom of persuing a "herd immunity" strategy such that the virus -- unable to find new victims -- peters out by itself when a majority of the population is immune.

"The only real solution for now is a vaccine," Archie Clements, a professor at Curtin University in Perth Australia, told AFP.

At the same time, laboratories are developing a slew of antibody tests to see what proportion of the population in different countries and regions have been contaminated.

Such an approach has been favoured in Britain and Finland, while in Germany some experts have floated the idea of an "immunity passport" that would allow people to go back to work.

"It's too premature at this point," said Saad Omer, a professor of infectious diseases at the Yale School of Medicine.

"We should be able to get clearer data very quickly -- in a couple of months -- when there will be reliable antibody tests with sensitivity and specificity."

One concern is "false positives" caused by the tests detecting antibodies unrelated to COVID-19.

The idea of immunity passports or certificates also raises ethical questions, researchers say.

"People who absolutely need to work -- to feed their families, for example -- could try to get infected," Balloux.

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