Drivers with Windows Down Exposed to 80% More Air Pollution

Statistics from the World Health Organization (WHO) show that air pollution kills an estimated seven million people throughout the globe every year and nine out of ten people are exposed to high levels of pollutants. A new study has shown that people who drive and ride in cars from the world’s least affluent cities are exposed to a disproportionate amount of in-car air pollution due to the fact that they rely heavily on opening their windows for ventilation.

A global team of researchers led by Surrey’s Global Centre for Clean Air Research(GCARE) investigated levels for commuters in ten different global cities in the following countries – India, Bangladesh, Brazil, Egypt, Columbia, Iraq, Tanzania, China, Malawi, and Ethiopia.

The team examined levels of two air pollution components – PM2.5 (fine particles that are 2.5 microns or smaller) and PM10 (fine particles that are 10 microns of less). PM2.5 is more harmful since the particles are smaller and have a higher probability of going deeper into the lungs and causing harm.

They investigated exposure levels inside vehicles during peak driving hours in the morning and evening in addition to off-peak hours in the middle of the day. They also measured how levels of exposure changed when drivers used re-circulation systems, fans or simply opened the windows of the car.

They discovered that drivers in some of the world’s poorest cities had higher levels of in-car pollution. Irrespective of the model of the car and the city, a windows-open setting indicated the highest exposure followed by fan-on and re-circulation. Exposure to pollution for windows-open during off-peak hours was 91% and 40% less than the morning and evening peak hours, respectively. The team also found that the windows-open setting exposed passengers to hotspots of air pollution for up to a third of the total length of travel.

The study showed that commuters who turn on the re-circulation are exposed to about 80% less harmful particles than those who open the windows of their car. Car cabin filters were more effective in removing pollution than fine particles which suggests that if new cars had more efficient filters it could lower the overall exposure of car commuters.

The team reports that we need as many cars as possible off roads or more green vehicles to reduce exposure to air pollution. However, this is a distant dream in many ODA (Official Development Assistance) countries. Cars that are air conditioned are unattainable for many vulnerable and poor commuters across the globe. The data is clear and coherent for all of the ten participating cities.

The team believes that they must now work with global partners to insure they have the information needed to put in place policies, programs and strategies to protect the most vulnerable in their communities and find realistic solutions to these serious problems.

The study has shown important conclusions that can help commuters make decisions throughout their day to day lives to protect their health. Even simple choices such as traveling during off-peak hours can go quite far in reducing their exposure to air pollution.

Through working with GCARE and global collaborators on the study, the team was given access to affordable technology to be able to collect novel data sets that had not been available for cities in the parts of the world they studied. They also got to see where the cities stood in comparison to other global cities in developing countries. This gave them the capability to share much needed knowledge and best practices.

To view the original scientific study click below

In-car particulate matter exposure across ten global cities.

Healthy Lifestyle for Cardiovascular Health also Promotes Good Eye Health

A new study has shown that ideal cardiovascular health which is typically indicative of a healthy lifestyle, was link with decreased odds of a person developing ocular diseases and especially diabetic retinopathy. The findings suggest that interventions to prevent cardiovascular diseases may also show promise in preventing diseases of the eye.

About 2.2 billion people worldwide suffer from ocular diseases which can lead to vision impairment and blindness. About one half of these cases could have been prevented. The leading causes of blindness or vision impairment are age related macular degeneration, cataract, diabetic retinopathy, and glaucoma.

Previous studies have founds associations between eye diseases and individual lifestyle factors such as obesity, smoking, or hypertension. It is well known that these particular metrics of ideal cardiovascular health do not work alone and may interact additively to result in diseases. Prior to the recent research, no other research has comprehensively evaluated the association of all of the metrics of ideal cardiovascular health with ocular diseases.

Most diseases of the eye show few symptoms at early stages, and a lot of people may not seek medical care despite the fact that there are readily available treatments. A recent online nationwide survey that consisted of all ethnic and racial groups in the U. S., showed that 88% of the 2,044 participants considered good vision to be very important to overall health. 47% of these participants rated losing their vision as the worst disease that could ever affect them. Surprisingly, 25% did not have any knowledge in regards to ocular diseases and their risk factors.

The study shows that following healthy lifestyle and behavioral habits can all contribute to good cardiovascular health as assessed by following the American Heart Association’s prescription for health metric known as Life’s Simple Seven (LS7). LS7 is based on the status of seven cardiovascular disease factors which are not smoking, healthy diet, regular physical activity, maintaining normal weight, controlling blood pressure, controlling cholesterol and controlling blood glucose levels.

Practicing these LS7 healthy lifestyles together was found to be associated with decreased odds for age related macular degeneration, cataract, diabetic retinopathy, and glaucoma. People with optimal cardiovascular health had 97% lower odds for diabetic retinopathy when compared to people with inadequate cardiovascular health.

Researchers evaluated data from 6,118 adults aged 40 or older who took part in the 2005-2008 National Health and Nutrition Examination Survey. The average age was 57 and 53% of whom were female. A one unit increase in LS7 scores was associated with reduced odds of age related macular degeneration, glaucoma and diabetic retinopathy.

Overall it is believed that the primary prevention and early detection of eye diseases are important when considering that over half of all deaths from ocular diseases and cardiovascular diseases are known to be preventable.

Considering the significant overlap of the risk factors of ocular and cardiovascular diseases, the research team recommends that screening for ocular diseases be incorporated into existing population based and clinical screenings for cardiovascular diseases. The hope is that the studies findings will encourage people to adhere to healthy lifestyle choices in order to prevent these age related disease while at the same time leading to increased collaborations between optometrists, ophthalmologists and cardiologists in order to better prevent cardiovascular and ocular diseases.

To view the original scientific study click below

The Association of Ideal Cardiovascular Health and Ocular Diseases Among US Adults.

Body Weight Has Surprising and Alarming Impact on Brain Function

According to a new brain imaging study, when a person’s weight goes up, all regions of the brain will go down in blood flow and activity. The study has revealed that being overweight or obese seriously impacts activity in the brain and increases the risk for Alzheimer’s Disease in addition to a variety of other cognitive and psychiatric conditions.

The study which is one of the largest studies to link obesity with brain dysfunction, included analysis of over 35,000 functional neuroimaging scans using single-photon emission computerized tomography (SPECT) from over 17,000 people to measure brain activity and brain flow. Low cerebral blood flow is the number one brain imaging predictor that a person will develop Alzheimer’s Disease. It is also linked to ADHD, depression, schizophrenia, bipolar disorder, addiction, traumatic brain injury, suicide and other psychiatric conditions.

Distinct patterns of progressively reduced blood flow was found in virtually every region of the brain across categories of normal weight, underweight, overweight, obesity and morbid obesity. The patterns were noted while the participants were in a resting state in addition to while they performed a concentration task.

Of particular interest, brain areas noted to be vulnerable to Alzheimer’s Disease (temporal and parietal lobes, posterior cingulate gyrus, precuneus and hippocampus) were found to have reduced blood flow along the spectrum of classifications of weight from normal weight to overweight, obese and morbidly obese. This is especially concerning news given that the latest statistics show that 72% of American are overweight and of whom 42% are obese.

The team has provided compelling evidence that obesity alters blood supply to the brain to shrink the brain and therefore promote Alzheimer’s disease. This is a very significant advance because it directly shows how the brain responds to our body.

The study highlights the real need to address obesity as a target for interventions that are designed to improve brain function. The team notes that one of the most important lessons learned is that brains can be improved when put in a healing environment through adopting brain healthy habits such as regular exercise and healthy calorie smart diets.

To view the original scientific study click below

Patterns of Regional Cerebral Blood Flow as a Function of Obesity in Adults.

Schooling and the Importance of Cognitive Health Throughout Life

Investing time in education during childhood and early adulthood not only expands career opportunities and can provide progressively higher salaries, but it also conveys benefits to longevity and health. It can also boost the cognitive skills people can develop earlier in life, pushing back the time at which age related dementia will begin to impact a person’s ability to care for themselves.

The new analysis has revealed that even though more extensive formal educations can forestall some of the more obvious signs of age related cognitive deficits, it does not lessen the rate of aging related cognitive declines. Instead, people who go further in school attain on the average a higher level of cognitive function in early and middle adulthood. This means the initial effects of cognitive aging are initially less obvious with the most severe impairments in cognitive health manifesting later than they might otherwise.

The total amount of formal education that people achieve is related to their average levels of cognitive functions throughout their adulthood. However, it is not appreciably related to their rates of aging related declines in their cognition.

This new conclusion refutes the previous long standing hypothesis that formal education during childhood through early adulthood will meaningfully protect against cognitive aging. Instead, the researchers concluded that people who have gone further with their education tend to decline from a higher peak level of cognitive function. They can therefore experience a longer period of cognitive impairment prior to dropping below what the team refers to as a “functional threshold”. This is the point where cognitive decline becomes so obvious that it will interfere with daily activities.

People vary in their rates of age related cognitive declines, however these differences are not appreciably related to educational levels.

For the study, the research team examined data from dozens of prior meta-analyses and cohort studies in an effort to better understand how educational levels affect both the changes in and levels of cognitive function in dementia and aging.

Although there are some uncertainties with their analysis, the team notes that a broader picture of how education relates to cognitive aging is emerging very clearly. During adulthood cognitive function in people with more years of education is on average higher than cognitive function in those with fewer years of education.

This analysis highlights the importance of formal education for cognitive development over the coarse of childhood, adolescence and early adulthood. According to the team, childhood education has important implications for the well being of people and societies not just during the employment years, but throughout life including old age.

This message from the team may be particularly relevant as governments decide if, when and how to reopen schools during the current COVID-19 pandemic. These decisions could have consequences for many decades in the future.

The research team has concluded that the conditions that shape development during the first decades of life carry great potential for the improvement of cognitive ability in early adulthood and for reducing public health burdens that are related to dementia and cognitive aging.

To view the original scientific study click below

Education and Cognitive Functioning Across the Life Span.

Implanted Neural Stem Cell Grafts and Functionality in Spinal Cord Injuries

Researchers at the University of California San Diego School of Medicine report that they have successfully implanted specialized grafts of neural stem cells directly into spinal cord injuries in mice. They then documented how the grafts grew and filled the site of injury, mimicking the mice’s existing neuronal network.

Almost 18,000 people in the U.S. suffer spinal cord injuries (SCIs) every year and another 294,000 people live with an SCI which is usually involving diminished physical function (such as difficulty breathing or bladder control) or some degree of permanent paralysis. It has long been the ambition of scientists to restore lost functions due to SCIs using stem cells.

Previous to the new study, neural stem cell grafts being developed in labs were sort of a black box. Although earlier research had shown improved functioning in SCI animal models following neural stem cell grafts, scientists were not quite sure what was happening.

Scientists knew that damaged host axons grow extensively into injury sites and that graft neurons in turn extended large numbers of axons into the spinal cord. However, they had no idea what kind of activity was occurring inside the graft itself and didn’t know if host or graft axons were actually making functional connections or if they only looked like they could.

The research team took advantage of recent technological advances which will allow researchers to both stimulate and record activity of genetically and anatomically defined neuron populations using light rather than electricity. This ensured the team would know exactly which host and graft neurons were at play without having to worry about electric currents spreading through tissue and potentially showing misleading results.

The team discovered that even in the absence of a specific stimulus, graft neurons fired spontaneously in very distinct clusters of neurons with highly correlated activity which was much like in the neural networks of the normal spinal cord. When they stimulated regenerating axons coming from the mice’s brain, they discovered that some of the same spontaneously active clusters of graft neurons responded robustly which indicated that those networks receive functional synaptic connections from inputs that typically drive movement. Sensory stimuli such as a pinch or light touch also activated graft neurons.

This showed that the team could turn on spinal cord neurons below the site of injury through stimulating graft axons extending into those areas. Through putting all these results together, it turns out that neural stem cell grafts have a remarkable ability to self-assemble themselves into spinal cord-like neural networks that functionally integrate with the host nervous system. Following years of inference and speculation, the team showed directly that each of the building blocks of a neuronal relay across injuries to the spine are in fact functional.

The team is now working on several avenues in an effort to enhance the functional connectivity of stem cell grafts such as organizing the topology of grafts to mimic those of the normal spinal cord with scaffolds and using electrical stimulation to strengthen the synapses between graft neurons and host.

While it may still be years off for the perfect combination of stem cells, stimulation, rehabilitation and other interventions, people are living with spinal cord injuries now. Therefore, the team is currently working with regulatory authorities to move their stem cell graft approach into clinical trials as soon as possible. They anticipate that if everything goes well, they could have a therapy within the next 10 years.

To view the original scientific study click below

Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury.

Re-engineering Antibodies for the Covid-19 Virus

Due to the millions of cases of COVID-19 reported worldwide, people are looking to antibody tests to see whether they have been exposed to the coronavirus that leads to the disease. Questions have arisen in regards to what exactly are antibodies and why are they important? People wonder if they have them are they immune to COVID-19 and if not why? Can a person be injected with antibodies as a treatment or preventative?

Antibody tests are conducted to see if there is a presence of antibodies which are specific proteins that are made in response to infections and they are disease specific. For example, measles antibodies will protect a person from getting the measles if they are exposed to the disease again, however they won’t protect a person from getting the mumps if they are exposed to the mumps.

Antibodies are very important as they prevent infection and heal patients that have been infected by diseases. If a person has antibodies they are immune to a disease as long as they remain in the person’s system. If someone does not have antibodies, then infection will proceed and the pandemic continues.

This foreign antibody based protection is known as passive immunity which is short term immunity provided when a person is given antibodies to a particular disease rather than producing these antibodies through their own immune system.

Research was conducted at The Catholic University of America in Washington D. C. by Victor Padilla-Sanchez into the initial steps of antibody protection. He specializes in viruses and uses computer models to understand the structure of viruses on the molecular level. This information is then used to try to understand how the virus functions.

SARS was the first new infectious disease identified in the 21st century. This particular respiratory illness originated in China in November 2002 and the WHO identified this new coronavirus (SARS-CoV) as the agent that led to this outbreak.

We are now in the middle of the new coronavirus (SARS-CoV-2) which emerged in Wuhan, China in 2019 and is known as COVID-19. To date there are no vaccines or therapeutics to fight this illness.

Both of these illnesses share the same spike protein, the entry key that allows the virus into human cells. The team’s idea was to take the antibodies found in the 2002 outbreak (80R and m396) and re-engineer them to fit the current COVID-19 virus.

Through using computer stimulation, Padilla-Sanchez discovered that differences in sequences prevent 80R and m396 from binding to COVID-19. Understanding why these antibodies did not bind to the SARS-CoV-2 spike protein might pave the way to engineering new antibodies that are effective. Mutated versions of the two antibodies can be produced and administered as a therapeutic to fight the disease and prevent infection.

Padilla-Sanchez’s docking experiments indicated that amino acid substitutions in 80R and m396 should increase binding interactions between the two antibodies and SARS-CoV-2 which would provide new antibodies to neutralize the virus. His next step is to prove it in the lab.

The docking experiments were ran on Stampede2 using Rosetta software suite which includes algorithms for computational modeling and analysis of protein structures. This software binds the proteins then provides a score for each binding experiment. If a good docking position can be found, then it can be recommended that this new, mutated antibody should go to production.

Currently a variety of labs across the globe are already testing vaccines. If a vaccine isn’t found in the near term we still have passive immunity which can prevent infection for several months as long as a person has the antibodies. Passive immunity might be a fast track in providing relief for the pandemic.

To view the original scientific study click below

In silico analysis of SARS-CoV-2 spike glycoprotein and insights into antibody binding.

Job Related Physical Stress Linked to Memory and Brain Decline

A recent study out of Colorado State University has discovered that physical stress at one’s job may be associated with poorer memory and faster brain aging. This study is the first evidence that links occupational stress to accelerated brain and cognitive aging.

It is well known that stress can speed up physical aging and is also a risk factor for many chronic illnesses. The research team looked at trying to understand how occupational exposures can affect the aging of our brains.

The average American worker spends more than eight hours per weekday at work. And most people will remain in the workforce for more than 40 years. By volume, occupational exposures outweigh the time spent on cognitive, leisure and physical activities which all help protect our aging brains and minds.

For their study the team connected responses to an occupational survey with brain imaging data from 99 cognitively normal older adults aged 60 to 79. They discovered that the participants who reported high levels of physical stress in their most recent job had smaller volumes in the hippocampus and also performed poorer on their memory tasks.

The link between physical stress and memory/brain were driven by physical demands at the workplace. These include excessive lifting of boxes onto shelves and reaching which are not necessarily aerobic activity. This is important because earlier work by the team showed that leisure aerobic activity is beneficial for the health of the brain and cognition from children to older adults. The researchers therefore controlled for the effects of leisure physical activity and exercise.

As was expected, leisure physical activity was linked with greater hippocampal volume, however the negative association with physical demands at the workplace persisted. This particular finding suggests that physical demands at the workplace may have parallel yet opposing links to brain health.

Most interventions for postponing decline in cognition focus on leisure and not on a person’s job. While it is unknown territory, the team believe future research can help people make some tweaks to their workplace environment for long term cognitive health.

The care of people with cognitive impairment is very costly on emotional, societal and economic levels. If brain health can be supported earlier in middle-aged workers, it could have a significant impact.

The team did consider and corrected for a variety of other factors that could be related to work environment, hippocampus and memory such as gender, age, educational level, brain size, years in the occupation, job title and general psychological stress.

Currently the research on this topic is fragmented. An earlier study linked mid-life managerial experience with greater hippocampus volume in older adults. Another study indicated that taxi drivers had larger hippocampi than city bus drivers which was presumed to be due to the need to navigate. In the current study, job complexity and psychological stress at work were not related to cognition and hippocampal volume. This study is just another piece of the puzzle.

To view the original scientific study click below

Occupational Physical Stress Is Negatively Associated With Hippocampal Volume and Memory in Older Adults.

Diets High in Plant Proteins Linked to Lower Death Risk

Researchers have linked a diet high in protein and especially high in plant proteins to a lower risk of death from any cause. The team says their findings support current dietary recommendations for people to increase their consumption of plant proteins in the general population.

Diets that are high in protein and especially proteins from plants such as whole grains, nuts and legumes (beans, lentils & peas) have been linked to lower risks of people developing heart disease, diabetes and stroke. Regular consumption of red meat and high intakes of other animal proteins have been associated with several health problems.

However, data on the link between different types of proteins and death are somewhat conflicting. The research teams based in the USA and Iran set out to measure the potential dose response relationship between the intake of total animal and plant proteins and the risk of death related to all causes, cancer and cardiovascular disease.

The team reviewed the results of 32 studies that have reported risk estimates for all cause, cancer and cardiovascular mortality in adults aged 19 and older. All of the studies were thoroughly assessed for any bias or problems in study design that might influence the results.

Mathematical models were used to compared the effects of the highest vs. the lowest categories of protein intakes. Analyses were done to evaluate the dose response relationship between mortality and protein intake.

During the follow-up period of up to 32 years, 113,039 deaths (22,303 from cancer and 16,429 from cardiovascular disease) occurred among 715,128 study participants. The results indicated that a high intake of total protein was linked to a lower risk of all cause mortality compared to a low intake.

The intake of plant proteins was linked to an 8% lower risk of all cause mortality and a 12% lower risk of cardiovascular disease mortality. The consumption of animal protein was not significantly linked to a risk of cancer and cardiovascular mortality.

A dose response analysis of data from 31 studies also indicated that an additional 3% of energy derived from plant proteins daily was linked to a 5% lower risk of death from all causes.

Possible explanations for the beneficial effects of plant proteins include their link to favorable changes in cholesterol, blood pressure and blood sugar levels which may help lower the risk of conditions such as type 2 diabetes and heart disease per the research team.

The team points to some limitations such as differences in the way studies analyzed the data and the possibility that some effects could have been due to confounding or unmeasured factors. Additionally, as most of the included studies were from Western nations, the team’s findings might not be applicable to other countries.

However, strengths from the study include the large number of participants and deaths which provides detailed insights into the link between the consumption of dietary protein and risk of mortality based on the current evidence.

The team’s findings have significant health implications as the consumption of plant proteins can be increased very easily by replacing animal proteins and could additionally have a large effect on longevity.

For anyone looking to increase their consumption of plant based proteins, the American Diabetes Association recommends eating foods such as beans, chickpeas, edamame beans, quinoa and lentils. And adding certain vegetables such as peas, spinach and broccoli can also be beneficial!

To view the original scientific study click below

Dietary intake of total, animal, and plant proteins and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies.

High Blood Sugar Levels May Reduce Benefits of Aerobic Exercise

Doctors encourage people to engage in regular aerobic exercise which is important for achieving and maintaining better overall health. A new study has however, discovered that some benefits of aerobic exercise might be dampened by higher than normal levels of blood sugar which is a condition known as hyperglycemia.

These diminished gains were seen in human and mouse models who had chronic hyperglycemia that is in the pre-diabetes range. The study has also shown that this maladaptive trait is independent of insulin levels in the blood and obesity.

Clinical studies have shown that people with chronically high levels of blood sugar or diabetes struggle to improve the capacity of their aerobic exercise compared to people who have normal blood sugar levels. The idea behind the current study was to see if induced high blood sugar in mice impairs their ability to improve their aerobic fitness. The team also looked to uncover the mechanisms that might lead to low fitness levels in people who had hyperglycemia.

The team used two mouse models that reflected the two major causes of hyperglycemia in people. One mouse group consumed a Western diet which is high in sugar and saturated fat which caused some weight gain along with hyperglycemia. The other mouse group was modified to produce less insulin which led to similar increases in blood sugar as the Western diet even though these mice ate a diet lower in fat and sugar and additionally maintained a normal body weight. Both mouse groups were subjected to a training protocol where they ran in wheels in their cages in order to boost their aerobic fitness.

In both hyperglycemic groups, the mice ran about 500 kilometers over the course of the study. However, on average they failed to improve their aerobic exercise capacity compared to mice with lower blood sugar levels. When the team looked at the skeletal muscle in these mice, they noted that the muscle was not adapting to the aerobic challenge as muscle normally would.

Muscle tissue has the ability to remodel itself which is one reason why exercise can become easier when done regularly. Over time, aerobic exercise such as swimming or running can alter muscle fibers to become more efficient at utilizing oxygen during exercise. Additionally, we grow new blood vessels which allows more oxygen to be delivered to the muscles which also helps increase our aerobic fitness levels.

The team proposes that the high levels of blood sugar might prevent muscle remodeling in part through modifying the extracellular matrix proteins found in the space between the muscles where blood vessels are formed.

Earlier research has demonstrated that a biological pathway called the JNK siginaling pathway can act as a kind of molecular switch which tells muscle cells to adapt to either strength or aerobic training. The team discovered that these JNK pathway signals were getting crossed in the hyperglycemic mice by activating pathways that as associated with strength training even though the mice were engaged in aerobic exercise. The results showed that the muscles of hyperglycemic mice have bigger fibers and fewer blood vessels which is more typical of strength training.

The team then followed up their findings on mice with clinical tests with young adult participants. They found that the participants who had higher blood sugar levels in response to the ingestion of glucose, a condition known as glucose tolerance, showed the lowest aerobic exercise capacity. When they looked at how their muscles responded to a single bout of aerobic exercise, they saw that the participants with the lowest glucose tolerance had the highest activation of the JNK signaling pathway which will block aerobic adaptations.

There is good news. Although the mouse models of hyperglycemia failed to improve their aerobic fitness with training they still achieved other important health benefits including improved glucose metabolism and decreased fat mass. Regular aerobic exercise if still a major recommendation for maintaining health in people with or without hyperglycemia. People who have hyperglycemia can benefit from other forms of exercise such as strength training which is also recommended for the maintenance of health.

The study does suggest a variety of approaches that may help people with chronic hyperglycemia eventually overcome obstacles to building aerobic capacity. One method is to adopt a diet that has been designed to keep blood sugar levels low. We sometimes believe that exercise and diet are separate ways to improve health. However, the team’s work shows that there is more interaction between these lifestyle factors than what has previously been known.

To view the original scientific study click below

Hyperglycaemia is associated with impaired muscle signalling and aerobic adaptation to exercise.

How Does a Stem Cell Know What to Become?

New findings from the University of Colorado Boulder may lead to new therapies for a variety of diseases including heart abnormalities and cancer. The study led researchers to becoming one step closer to answering the fundamental question as to how a stem cell, which is the raw material with which our tissue cells and organs are made of, knows what to become?

Deep inside our cells each one has an identical genome, a complete set of genes which provides the instructions for our cells’ function and form. If every blueprint is identical, then why does an eye cell act and look differently than a brain cell or skin cell?

The research team concluded that the molecular messenger RNA plays an indispensable role in differentiation of cells serving as a bridge between our genes and the “epigenetic” machinery that turns them on and off. When this bridge is flawed or missing, a stem cell on the way to becoming a heart cell will not learn to beat.

The research comes at a time when pharmaceutical companies are taking a huge interest in RNA. Although the new research is young, it is thought it could ultimately inform development of new RNA targeted therapies ranging from therapies for cardiac abnormalities and cancer treatments.

All genes are not expressed in all cells all the time. Instead, each type of tissue has its own epigenetic program that will determine which genes get turned on or turned off at any time. The team determined that RNA is a master regulator of this epigenetic silencing. In the absence of RNA, this system does not work and it is critical for life.

Scientists have known for a long time that while each cell has identical genes, cells that reside in different tissues and organs express them differently. Epigenetics, the machines that switches them on or off, makes this possible. But just how this machinery works has not been clear.

In 2006 John Rinn who is now a professor of biochemistry at CU Boulder and Thomas Cech, the co-senior-author of the new paper, proposed for the first time that RNA might be the key. In a landmark paper published in Cell, Rinn showed that inside the nucleus, RNA attaches itself to a folded cluster of proteins known as polycomb repressive complex (PRC2) which is thought to regulate gene expression. A variety of other studies have since found the same and have added that different RNAs also bind to different protein complexes.

The hot debate question became, does this actually matter in determining a cell’s fate? No less than 502 papers have been published since. Some indicated that RNA is key in epigenetics. Others dismissed its role as tangential at best.

In 2015 a biochemist and postdoctoral researcher named Yicheng Long in Thomas Cech’s lab set out to ask this same debate question again using the latest available tools. After a meeting at the BioFrontiers Institute where both labs are housed, Long ran into a computational biologist in Rinn’s lab. They formed a unique partnership.

They were able to use data science approaches and high powered computing to understand molecular patterns and evaluate RNA’s role in a new, quantitative approach. In the lab they used a simple enzyme to remove all RNA in cells in an effort to understand whether the epigenetic machinery was still able to find it way to DNA to silence genes. Their answer was “no”.

It appeared RNA was playing the role of an air traffic controller, that is guiding the plane or protein complex to the correct spot on the DNA to land and then silence genes. For a third step, the team used the gene editing technology CRISPR to develop a line of stem cells that were destined to become human heart muscle cells but in which the PRC2 was incapable of binding to RNA. In other words, the plane could not connect with air traffic control and therefore lost its way and the process fell apart.

At day 7, the normal stem cells had started to look and act like heart cells. However the mutant cells did not beat. However, when normal PRC2 was restored, they began to act more normally. The team says they can now say without a doubt that RNA is critical in the process of cell differentiation.

Earlier research has shown that genetic mutations in humans which disrupt RNA’s ability to bind to these proteins, heightens the risk of fetal heart abnormalities and certain cancers. Ultimately the researchers see a day when RNA targeted therapies can be used to address such problems.

The new findings set a new scientific stage which shows an inextricable link between RNA biology and epigenetics. They could have significant implications for understanding and then addressing human disease in the future.

To view the original scientific study click below

RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells.