Cure for HIV moves closer as scientists find potential genetic switch

Agencies
December 7, 2018

Washington, Dec 7: A genetic switch that causes HIV hidden inside the cells to replicate can be manipulated to completely eradicate the virus from the human body, a study has found.

Cells harbouring latent HIV are "invisible" to the natural defences of the immune system, said researchers from the University of Illinois at Chicago in the US.

During infection, the DNA of HIV makes its way into the host cell's nucleus and integrates itself into the host genome.

The Tat gene circuit is a key piece of HIV DNA that controls the HIV gene transcription and activation, according to the study published in the journal Proceedings of the National Academy of Sciences.

When activated, it initiates a takeover of the cell's machinery to churn out new copies of the HIV virus, which eventually burst from the cell and infect neighbouring cells.

HIV-specific immune effector cells kill cells infected with HIV, but only when the cells are being used to produce more of the virus, meaning that the Tat gene circuit is switched on.

In cells that are latently infected, the Tat gene circuit is off, and the cell goes about its normal business all the while harbouring quiescent HIV.

"By targeting the Tat gene circuit with drugs or small molecules to activate it, we would be able to cause latently-infected cells to start producing more virus, and then they can be destroyed by the immune system," said Jie Liang, a professor at the University of Illinois.

So far, there are no drugs successfully targeting this circuit, researchers said.

People infected with the HIV virus can live relatively normal lives with exceedingly low or even undetectable viral loads thanks to powerful antiretroviral therapies that work to suppress viral replication.

However, even in people where the virus is undetectable, it doesn't mean it's completely absent.

The HIV virus can hide in cells in an inactivated state, meaning it isn't actively replicating.

This is a dire situation and makes life-long antiretroviral therapy the only option for HIV infected patients.

"It is extremely difficult to flush latently-infected cells out of their latency," Liang said.

Techniques developed to reactivate latent HIV-infected cells so that they become susceptible to the body's natural immune response or to drug therapies have had mixed results.

This is mostly because the technique, known as "shock and kill," relies on a class of drugs called HDAC inhibitors that come with severe adverse effects, researchers said.

"We need to better understand the mechanisms that regulate HIV latency so we can identify new opportunities for intervention and develop better drugs that can either lock viral particles in a latent state, or kill latent cells, or both," Liang said.

The Tat gene circuit has a random probability of being active or inactive, and the switch from inactive to active can happen spontaneously.

"In HIV-infected cells, reactivation of the Tat gene circuit is still a very rare event," Liang said.

The researchers developed advanced computational algorithms to study the Tat gene circuit under different conditions.

"Using different models and algorithms, we were able to accurately map a 'probability landscape' of the cellular reactions that can impact Tat gene circuit reactivation, and our results suggest new ways of targeting latent cells that may lead to the eradication of the HIV virus from a host," Liang said.

Researchers identified ways to manipulate the Tat gene circuit so that the "shock and kill" technique would be more effective.

They also looked at a "block and lock" strategy, where latent viral particles are locked into latency by permanently blocking activation of the Tat gene circuit.

"Our results suggest that by controlling HIV latency through manipulation of the Tat gene circuit, effective therapeutic strategies can be identified that would one day provide a cure for HIV," Liang said.

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Agencies
February 20,2020

The health and future of every child and adolescent worldwide is under immediate threat from ecological degradation, climate change and exploitative marketing practices that push fast food, sugary drinks, alcohol and tobacco at children, said a new report on Wednesday.

No single country is adequately protecting children's health, their environment and their futures, according to the report by a commission of over 40 child and adolescent health experts from around the world.

The commission, convened by the World Health Organization (WHO), the United Nations children's agency, Unicef, and medical journal the Lancet, found that while the poorest countries need to do more to support their children's ability to live healthy lives, excessive carbon emissions --disproportionately from wealthier countries -- threaten the future of all children.

"Despite improvements in child and adolescent health over the past 20 years, progress has stalled, and is set to reverse," said former Prime Minister of New Zealand and Co-Chair of the Commission, Helen Clark.

"It has been estimated that around 250 million children under five years old in low- and middle-income countries are at risk of not reaching their developmental potential, based on proxy measures of stunting and poverty. But of even greater concern, every child worldwide now faces existential threats from climate change and commercial pressures," Clark said.

The report, titled "A Future for the World's Children?", includes a new global index of 180 countries, comparing performance on child flourishing and sustainability, with a proxy for greenhouse gas emissions, and equity, or income gaps.

India ranked 131 among the 180 countries in the index.

The index shows that children in Norway, the Republic of Korea, and the Netherlands have the best chance at survival and well-being, while children in the Central African Republic, Chad, Somalia, Niger and Mali face the worst odds.

However, when the authors took per capita CO2 emissions into account, the top countries trail behind: Norway ranked 156, the Republic of Korea 166, and the Netherlands 160.

Each of the three emits 210 per cent more CO2 per capita than their 2030 target.

The US, Australia, and Saudi Arabia are among the ten worst emitters.

If global warming exceeds 4 degree Celsius by the year 2100 in line with current projections, this would lead to devastating health consequences for children, due to rising ocean levels, heatwaves, proliferation of diseases like malaria and dengue, and malnutrition, said the report.

The only countries on track to beat CO2 emission per capita targets by 2030, while also performing fairly (within the top 70) on child flourishing measures are: Albania, Armenia, Grenada, Jordan, Moldova, Sri Lanka, Tunisia, Uruguay and Vietnam.

The report also revealed the distinct threat posed to children from harmful marketing. Evidence suggests that children in some countries see as many as 30,000 advertisements on television alone in a single year, while youth exposure to vaping (e-cigarettes) advertisements increased by more than 250 per cent in the US over two years, reaching more than 24 million young people.

Children's exposure to commercial marketing of junk food and sugary beverages is associated with purchase of unhealthy foods and overweight and obesity, linking predatory marketing to the alarming rise in childhood obesity, said the report.

The number of obese children and adolescents increased from 11 million in 1975 to 124 million in 2016 - an 11-fold increase, with dire individual and societal costs.

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Agencies
July 8,2020

Probiotics that broaden the mix of helpful bacteria in the gut may help to ease depression, say researchers.

Foods that broaden the profile of helpful bacteria in the gut are collectively known as probiotics. These "good bacteria" can be taken as supplements, or found naturally in yoghurts or fermented foods.

For the findings, the research team from the University of Brighton in the UK searched for relevant studies published in English between 2003 and 2019, which looked at the potential therapeutic contribution of pre-and probiotics in adults with depression and/or anxiety disorders.

Out of an initial haul of 71 studies, just seven met all the criteria for inclusion. All 7 investigated at least one probiotic strain; four looked at the effect of combinations of multiple strains.In all, 12 probiotic strains featured in the selected studies, primarily Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidium.

One study looked at combined pre-probiotic treatment, while one looked at prebiotic therapy by itself. The studies varied considerably in their design, methods used, and clinical considerations, but all of them concluded that probiotic supplements either alone or in combination with prebiotics may be linked to measurable reductions in depression.

And every study showed a significant fall or improvement in anxiety symptoms and clinically relevant changes in biochemical measures of anxiety or depression with probiotic or combined pre-probiotic use.

Of the 12 different probiotics investigated, 11 were potentially useful, the findings showed.'Probiotics may help reduce the production of inflammatory chemicals, such as cytokines, as is the case in inflammatory bowel disease, the researchers suggested.

"They may help direct the action of tryptophan, a chemical thought to be important in the gut-brain axis in psychiatric disorders," they added.

In this way, with a better understanding of the mechanisms, probiotics may prove to be a useful tool across a wide range of conditions," the authors wrote.

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News Network
July 9,2020

Washington, Jul 9: Ayurvedic practitioners and researchers in India and the US are planning to initiate joint clinical trials for Ayurveda formulations against the novel coronavirus, the Indian envoy here has said.

In a virtual interaction with a group of eminent Indian-American scientists, academicians, and doctors on Wednesday, Indian Ambassador to the US Taranjit Singh Sandhu said the vast network of institutional engagements have brought scientific communities between the two countries together in the fight against Covid-19.

 “Our Institutions have also been collaborating to promote Ayurveda through joint research, teaching and training programs. Ayurvedic practitioners and researchers in both the countries are planning to initiate joint clinical trials of Ayurvedic formulations against Covid-19,” Sandhu said.

“Our scientists have been exchanging knowledge and research resources on this front,” he said.

The Indo-US Science Technology Forum (IUSSTF) has always been instrumental in promoting excellence in science, technology, and innovation through collaborative activities.

To address Covid-19-related challenges, the IUSSTF had given a call to support joint research and start-up engagements. A large number of proposals are being reviewed on fast track mode by the experts on both the sides, he said.

“Indian pharmaceutical companies are global leaders in producing affordable low-cost medicines and vaccines and will play an important role in the fight against this pandemic,” Sandhu said.

According to the ambassador, there are at least three ongoing collaborations between Indian vaccine companies with US-based institutions.

These collaborations would be beneficial not just to India and the US, but also for the billions who would need to be vaccinated against Covid-19 across the world, he noted.

Asserting that innovation will be the key driver in pandemic response and recovery, he said tech-companies and start-ups have already begun to take the lead in this direction.

"Telemedicine and telehealth will evolve as will other digital platforms across sectors," he said.

Noting that there has been a longstanding collaboration between India and the US in the health sector, he said scientists have been working together in several programs to understand important diseases at the basic and clinical level.

Many such programs have been focused on translational research to develop new therapeutics and diagnostics.

There are over 200 ongoing NIH funded projects in India involving 20 institutions from NIH network and several eminent institutions in India engaged in a wide spectrum of research areas to create health care solutions, the senior diplomat said.

The collaboration under Vaccine Action Program (VAP) resulted in the development of ROTAVAC vaccine against rotavirus which causes severe diarrhea in children.

The vaccine was developed by an Indian company (Bharat Biotech) at an affordable cost. It has been commercialised and introduced in the Expanded Program on Immunisation.

Development of many other vaccines such as TB, Influenza, Chikungunya are also in progress under the VAP, he said.

 “As I speak, the VAP meeting is in progress where experts from both countries are deeply engaged in technical discussions to expedite development of Covid-19 vaccine,” Sandhu said in his remarks.

During the interaction, the eminent experts appreciated India's handling of the Covid-19 pandemic and offered their valuable suggestions and best practices in this regard.

They shared their ideas on deepening the knowledge partnership between India and the US.

The experts who took part in the interaction, were drawn from wide-ranging fields including artificial intelligence, quantum information science, biomedical engineering, robotics, mechanical engineering, earth and ocean science, virology, physics, astrophysics, and health sciences.

Prominent among those who attended the virtual interaction were Subhash Kak Regents Professor at Oklahoma State University, Dr Vijay Kuchroo, Samuel L Wasserstrom Professor of Neurology at Harvard Medical School, Dr Ashish M Kamat, Professor of Urology at MD Anderson Cancer Center, Ashutosh Chilkoti, Alan L Kaganov Professor of Biomedical Engineering and Chair of the Department of Biomedical Engineering at Duke University; and Prof Manu Prakash, a professor in Department of Bioengineering at Sandford University, among others.

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