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A collection of human DNA variants tied to more severe cases of COVID-19 are also associated with other serious medical conditions such as those dealing with blood clots and faulty inflammatory responses, according to a new study. A summary of this analysis, which comes from stored genetic data from 600,000 people, is published in PLOS Genetics.

This work provides invaluable insights into the genetic architecture of COVID-19 risk factors and disease complications, a pressing need as the pandemic continues, says the studys lead author, Anurag Verma, an instructor in translational medicine and human genetics at the Perelman School of Medicine. The balance between the associations that we uncovered will be important as more therapies for COVID-19 are considered.

Data used in this study comes from the Million Veteran Program, which was established by the U.S. Department of Veterans Affairs. It is among the largest and most diverse biobanks (repositories of genetic information used for research) in the world, making it ideal for examining the various pieces of DNA that could be exploited by COVID-19.

With the variants associated with severe COVID-19 in hand, the researchers examined whether any other health conditions were more likely to be associated with them. To do this, they analyzed roughly 1,500 phenotypes, meaning the identifiable traits of a disease, which could be gleaned from an electronic health record.

Variants that had been associated with more severe COVID-19 in the ABO locus, a term meaning a genes position on a chromosome, were found to also be associated with the most other conditions. Patients with these variants were 33% more likely to have conditions like venous embolism and thrombosis, which both involve blood clots.

Some differences in association were seen when genetic ancestry was taken into account. The odds of someone having neutropeniaa condition in which a patient has a low count of the white blood cells used by the bodys immune systemwere 29% higher in those with African genetic ancestry who had variants in the LMNA locus. Those with European genetic ancestry who had the same variants did not share a higher association.

This story is by Frank Otto. Read more at Penn Medicine News.

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DNA analysis finds links between severe COVID and other conditions | Penn Today - Penn Today

It could be in their genes, posits Tangye. Genetic influences are either making people vulnerable to really severe disease but may also contribute to resistance there are populations of people who probably should have been infected and sick but werent.

Exactly which genes have a protective effect is part of an international research project called the COVID Human Genetic Effort, that Christodoulou is involved with.

We are collecting information and DNA from individuals who have been hyperexposed to COVID but who dont seem to contract COVID for example, living in a household where multiple family members were infected, but one member of the household wasnt to see if genetic factors can be identified that might offer protection against COVID infection, says Christodoulou, who is also the chair of Genomic Medicine at the University of Melbourne.

While researchers keep searching for the genetic clues, a new study published at the end of April, found booster shots can increase the range of immune cells, called memory B cells, making them more effective at neutralising COVID.

With any infection or vaccination, our body responds and then forgets the virus, explains Tangye, but becomes better at responding with repeated exposure. The first and second doses are like the training, getting your immune system into good shape and ready to take off and the third really gives you the protection you are primed and ready to go.

So if someone who has recently been vaccinated is exposed to COVID, they may be protected. If they have been boosted, this may provide even more protection, at least for a time.

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The degree of exposure how long we were in contact with someone and whether we were inside or out will also make a difference, as will our behaviour.

People have become much more cognisant of social distancing and washing their hands and wearing masks. There are those non-pharmaceutical interventions people have embraced, Tangye says.

As for how healthy you are generally, that unfortunately wont make us resistant to catching COVID.

We regularly hear of otherwise young, fit and healthy individuals contracting very severe COVID, says Christodoulou. For those otherwise healthy people we know that there are some factors that are associated with this, e.g., having so-called auto-antibodies to type 1 interferons (type 1 interferons are the first line of defence against COVID) or having mutations in genes that are involved in production and function of type 1 interferons.

Being healthy is good. But healthy people are still getting sick. Its not a panacea.

Interestingly, Tangye adds that there are people who naturally have this type 1 interferon pathway turned up a little bit: That can be pathogenic they can get these inflammatory diseases that dont have a defined triggerthese non-infectious, spontaneous flares for no good reason but people with those conditions may well have some resistance to COVID just because they have that innate immune response primed.

These people account for only a fraction of never COVIDs. For the rest, it seems to come down to a combination of immunity, genetics, environment and luck.

Being healthy all round puts you in better shape against infectious diseases and lifestyle disease, says Tangye. Being healthy is good. But healthy people are still getting sick. Its not a panacea.

Most of us may not be able to do much to avoid the virus, but we can still look to never COVIDs for some answers.

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If we can identify genetic reasons why people dont get COVID, it may help inform ways by which SARS COV2 enters or attacks our cells remember viruses are hopeless on their own. They need all the machinery of our cells to be disease-causing, explains Tangye.

So if we can disrupt the human cell processes without too many adverse events we could be better at stopping viral infection.

Make the most of your health, relationships, fitness and nutrition with our Live Well newsletter. Get it in your inbox every Monday.

Continued here:
Havent had COVID yet? Its got to do with more than your T cells - WAtoday

It could be in their genes, posits Tangye.

Genetic influences are either making people vulnerable to really severe disease but may also contribute to resistance there are populations of people who probably should have been infected and sick but werent.

Exactly which genes have a protective effect is part of an international research project called the COVID Human Genetic Effort, that Christodoulou is involved with.

We are collecting information and DNA from individuals who have been hyperexposed to COVID but who dont seem to contract COVID for example, living in a household where multiple family members were infected, but one member of the household wasnt to see if genetic factors can be identified that might offer protection against COVID infection, says Christodoulou, who is also the chair of Genomic Medicine at the University of Melbourne.

While researchers keep searching for the genetic clues, a new study published at the end of April, found booster shots can increase the range of immune cells, called memory B cells, making them more effective at neutralising COVID.

With any infection or vaccination, our body responds and then forgets the virus, explains Tangye, but becomes better at responding with repeated exposure. The first and second doses are like the training, getting your immune system into good shape and ready to take off and the third really gives you the protection you are primed and ready to go.

Loading

So if someone who has recently been vaccinated is exposed to COVID, they may be protected. If they have been boosted, this may provide even more protection, at least for a time.

The degree of exposure how long we were in contact with someone and whether we were inside or out will also make a difference, as will our behaviour.

People have become much more cognisant of social distancing and washing their hands and wearing masks. There are those non-pharmaceutical interventions people have embraced, Tangye says.

As for how healthy you are generally, that unfortunately wont make us resistant to catching COVID.

We regularly hear of otherwise young, fit and healthy individuals contracting very severe COVID, says Christodoulou. For those otherwise healthy people we know that there are some factors that are associated with this, e.g., having so-called auto-antibodies to type 1 interferons (type 1 interferons are the first line of defence against COVID) or having mutations in genes that are involved in production and function of type 1 interferons.

Being healthy is good. But healthy people are still getting sick. Its not a panacea.

Interestingly, Tangye adds that there are people who naturally have this type 1 interferon pathway turned up a little bit: That can be pathogenic they can get these inflammatory diseases that dont have a defined triggerthese non-infectious, spontaneous flares for no good reason but people with those conditions may well have some resistance to COVID just because they have that innate immune response primed.

These people account for only a fraction of never COVIDs. For the rest, it seems to come down to a combination of immunity, genetics, environment and luck.

Being healthy all round puts you in better shape against infectious diseases and lifestyle disease, says Tangye. Being healthy is good. But healthy people are still getting sick. Its not a panacea.

Most of us may not be able to do much to avoid the virus, but we can still look to never COVIDs for some answers.

Loading

If we can identify genetic reasons why people dont get COVID, it may help inform ways by which SARS COV2 enters or attacks our cells remember viruses are hopeless on their own. They need all the machinery of our cells to be disease-causing, explains Tangye. So if we can disrupt the human cell processes without too many adverse events we could be better at stopping viral infection.

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Are COVID-resistant people healthier or is it in their genes? - News Azi

image:Researchers at North Carolina State University have demonstrated that neuron-like cells derived from human stem cells can serve as a model for studying changes in the nervous system associated with addiction. The work sheds light on the effect of dopamine on gene activity in neurons, and offers a blueprint for related research moving forward. This image shows stem cell-derived medium spiny-like neuron morphology highlighted by the green fluorescent protein GFP and neuron marker MAP2 in red. view more

Credit: Ryan Tam, NC State University

Researchers at North Carolina State University have demonstrated that neuron-like cells derived from human stem cells can serve as a model for studying changes in the nervous system associated with addiction. The work sheds light on the effect of dopamine on gene activity in neurons, and offers a blueprint for related research moving forward.

It is extremely difficult to study how addiction changes the brain at a cellular level in humans nobody wants to experiment on somebodys brain, says Albert Keung, corresponding author of the study and an assistant professor of chemical and biomolecular engineering at NCState. What weve done here demonstrates that we can gain a deep understanding of those cellular responses using neuron-like cells derived from human stem cells.

At issue is how cells in our nervous system respond to drugs that are associated with substance abuse and addiction. Our bodies produce a neurotransmitter called dopamine. Its associated with feelings, such as pleasure, that are related to motivation and reward. When neuronal cells in the brains reward pathway are exposed to dopamine, the cells activate a specific suite of genes, triggering the feelings of reward that can make people feel good. Many drugs from alcohol and nicotine to opioids and cocaine cause the body to produce higher levels of dopamine.

In experiments using rodents, researchers have shown that when relevant neuronal cells are exposed to high levels of dopamine for an extended period of time, they become desensitized meaning the cells gene activation is less pronounced in response to the dopamine, Keung says. This is called gene desensitization. However, until now, it hasnt been possible to do an experimental study using human neuronal cells.

Our work here is the first experimental study to demonstrate gene desensitization in human neuronal cells, specifically in response to dopamine, says Ryan Tam, first author of the study and a Ph.D. student at NCState. We dont have to infer that it is happening in human cells; we can show that it is happening in human cells.

In their study, Tam and Keung exposed neuron-like cells derived from human stem cells to varying levels of dopamine for varying periods of time. The researchers found that when cells were exposed to high levels of dopamine for an extended period of time, the relevant reward genes became significantly less responsive.

This is an interesting finding, but its also a proof of concept study, Tam says. Weve demonstrated that gene desensitization to dopamine occurs in human cells, but there is still a lot we dont know about the nature of the relationship between dopamine and gene desensitization.

For example, could higher levels of dopamine cause desensitization at shorter time scales? Or could lower levels of dopamine cause desensitization at longer time scales? Are there threshold levels, or is there some sort of linear relationship? How might the presence of other neurotransmitters or bioactive chemicals affect these responses?

Those are good questions, which future research could address, says Keung. And weve demonstrated that these neuron-like cells derived from human stem cells are a good model for conducting that research.

The paper, Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization, is published open access in the journal Cells. The work was done with support from an NIH Avenir Award in Genetics and Epigenetics of Substance Abuse, under grant number 1DP1DA044359. The Avenir Award program represents the National Institute onDrug Abuse's commitment to supporting researchers who represent the future of addiction science.

Experimental study

Cells

Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization

21-Apr-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Stem cell-derived model provides insights on gene activity and addiction - EurekAlert

It's been a big month for Perseverance. In addition to reaching Jezero Delta and breaking distance records, (per Space), it also captured the best ever recording of a solar eclipse from the surface of the red planet.

On April 2, 2022, Mars's moon Phobos passed in front of the Sun, looking an awful lot like the slowly wandering eye of Sauron. In addition to just looking really cool, the observations can help scientists to better understand the gravitational relationship between Mars and its two moons, (per NASA).

Perseverance used its Mastcam-Z camera system which is intended to take panoramic and 3D images of the Martian environment while the rover makes its way along the surface. While NASA has captured several eclipses from the Martian surface in the past, going all the way back to Spirit and Opportunity, the Mastcam-Z provided full color, the highest zoom, and best frame rate to date.

As explained by NASA, Phobos is only about 17 miles across at its widest point and it moves pretty fast, orbiting Mars three times per day. As a result, the eclipse was relatively brief, lasting only about 40 seconds.

It's good that we're getting these images while we can. The gravitational relationship between Mars and Phobos is such that eventually, the moon will crash to the planet's surface. Luckily, that won't happen for tens of millions of years.

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The 12 Coolest Scientific Discoveries Of April 2022 - SlashGear