StemCell Therapy

At the molecular level all cancers are genetic, they start as your normal breast cell or ovaries and overtime pick up small genetic changes. When talking about inherited testing or hereditary testing only a small portion of cancer can be passed down in a family. We roughly quote 5-10% can be due to hereditary reasons or something we might find in an inherited genetic test, explained Dr. Tong at the CURE Educated Patient Womens Cancer Summit.

Genetic testing is a critical part of understanding these cancers, as well as how to treat, and Ill be discussing today about how we think about how genetics fits in cancer development, how genetic testing plays a role and how genetic counseling can help induvial and families come to decisions around genetics, says Dr. Tong.

Some exceptions include, up to 20% of negative breast cancers that can be hereditary and up to 25% of ovarian cancers can be hereditary, which is why genetic testing is recommended for all ovarian cancers.

When talking about hereditary cancer Dr. Tong says clinicians and genetic counselors are thinking about if that person has a higher chance of developing cancer, because nobody is at a 0% of developing cancer. Genetic testing will look at to see if they can identify what is elevating the persons risk of developing cancer, and can you potentially explain why a person developed certain cancer.

Part of what we learn from genetic testing, is not only could it have been due to a hereditary cause, such as a mutation in a gene, but which gene mutation and how can we differentially take care of people depending on which gene mutation did cause that, says Dr. Tong.

Guidelines recommend that all women diagnosed with epithelial ovarian cancer and breast cancer should be offered genetic testing.

Beginning in 2015 technology has brought three different types of gene testing or as they call it, Multi-Gene Panel Testing. Then there is a decision about how much genetic testing to do. For genes that they know are associated with inherited risk, those are high and moderate risk genes, they have actionable guidelines for treatment, risk reduction or prevention.

As technology develops you think about if the low-risk genes should also be looked at, the most likely have no impact on your health, such as a recessively inherited cancer risk, the information from these genes may be relevant to your family members or future generations. Some panel offers looking at newly described genes, they have limited evidence that they may impact inherited cancer risk, and they dont have actionable guidelines yet but could in the future.

We think that pretest counseling with a genetic counselor can help an induvial better understand how genetics impacts or plays a role in their cancer diagnosis or in their family history. Genetic counselors will take a look at family history and go many generations to look at distant relatives to see if there is a pattern to the cancers of that family that can be inherited, or does it look more like sporadic risks, then that counselor can discuss what the testing options are, how much testing to have or if its even right for you or not, says Dr. Tong about genetic testing counseling.

Types of results include a negative, the most important to be working with a genetic counselor, meaning there was no change found in the gene, it is considered a normal result and cancer treatment, screening and prevention decisions can be based on personal and family history of cancer. The next is a variant or uncertain significance, also considered a normal result, a change was found but is most likely due to normal human variation. The last result is positive result, where they find a change or genetic mutation that is associated with cancer, cancer treatment, screening and prevention decisions will be based on the risks specific to the change found.

Some may fear that they may be discriminated against due to their genetic testing results. There are laws in place that will protect you and your family members from employment or health insurance discrimination such as the Genetic Information Non-Discrimination Act of 2008, or GINA. In addition, there is the Americans with Disabilities Act, ADA, and the Health Information Portability and Accountability Act, HIPPA. However, there are limitations, how these laws dont protect against other types of discrimination such as life insurance, disability or long-term care, which would be discussed in your genetic counseling session.

Genetic testing can help thinking about what the path forward is for you and your family when we do learn the results, Dr. Tong concludes. He says going to a genetic counselor can help medically keep you healthy and also emotionally, connecting you with different resources and support organizations.

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What is Genetic Cancer Testing and How Do Patients Get Tested? - Curetoday.com

Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.

Antibodies Respond Differently to Severe Versus Mild COVID-19

Researchers at Stanford Medicine found that COVID-19 antibodies preferentially target different parts of the SARS-CoV-2 virus in mild COVID-19 cases than they do in severe cases. In addition, they fade differently based on the severity of the case. People with severe COVID-19 have low proportions of antibodies that target the spike protein. In milder cases, the antibodies seem to do a better job of binding to the spike protein. The spike protein binds to the ACE2 receptor on human cells, which allows the virus to enter the cell. Once inside, the virus gets rid of its outer coat, takes over the cells protein-making machinery and churns out more viral particles that then infect other cells. Antibodies that bind to the spike protein block the ability to bind to ACE2. Antibodies that bind to other parts of the virus dont seem to prevent viral spread.

Antibody responses are not likely to be the sole determinant of someones outcome, said Scott Boyd, associate professor of pathology at Stanford. Among people with severe disease, some die and some recover. Some of these patients mount a vigorous immune response, and others have a more moderate response. So, there are a lot of other things going on. There are also other branches of the immune system involved. Its important to note that our results identify correlations but dont prove causation.

Understanding Brain Plasticity in Adults

When brains develop, they constantly grow new neuronal connectionssynapsesas they learn and remember. Important connects are nurtured and reinforced while seemingly unnecessary ones are pruned. Adult brains undergo similar treatment, but its not well understood why adult synapses are eliminated. A group of researchers at The Korean Advanced Institute of Science and Technology (KAIST) have found the underlying mechanism of plasticity, which could be related to neurological disorders in adult brains. The brains gray matter contains microglia and astrocytes. Microglia are a frontline immune defensethey eat pathogens and dead cells. Astrocytes are star-shaped cells that help structure the brain and maintain homeostasis with involvement in neuronal signaling. It was long thought that microglial eat synapses as part of their clean-up effort, a process called phagocytosis. But their research, using a new molecular sensor, found that it was actually the astrocytes that are constantly eliminating excessive and unnecessary adult excitatory synaptic connections.

New Class of Antibiotic Works Against Range of Bacteria

Investigators withThe Wistar Institute have identified a new class of antibiotics that have a broad range of antibacterial effects, including against microbes with antimicrobial resistance (AMR). They focused on a metabolic pathway essential for bacteria but absent in humans, called methyl-D-erythritol phosphate (MEP) or non-mevalonate pathway, which is responsible for biosynthesis of isoprenoids. Isoprenoids are required for cell survival in most pathogenic bacteria. The researchers targeted the IspH enzyme, essential in isoprenoid biosynthesis. They screened several million commercially available compounds using computer models to find ones that could bind with the enzyme and chose the most potent ones. Most IspH inhibitors cant penetrate the bacterial cell wall, so the researchers worked to identify and synthesize novel IspH inhibitors that could get inside the bacteria.

Rhesus Macaque Genome Reference Includes 85 Million Genetic Variants

Researchers at Baylor College of Medicine, the University of Missouri and the University of Washington created a new reference genome assembly, identifying more than 85 million genetic variants in the rhesus macaque. This makes it the largest database of genetic variation for any single nonhuman primate species. It is a big improvement over the first reference assembled in 2007, and they believe it can help analyze and answer fundamental questions in molecular genetics, cell biology and physiology, not just in rhesus macaques, but in humans and other primates and mammals.

This is a major step forward in the amount of information we have about genetic variation in the rhesus macaque, said Jeffrey Rogers, associate professor at the Human Genome Sequencing Center and Department of Molecular and Human Genetics at Baylor. We have actually identified thousands of new mutations in the population of research animals. Now colleagues all over the country who are investigating various aspects of health and disease using rhesus macaques can begin to make use of that information.

Common Diabetes Drug Linked to Rare COVID-19 Complications

Although diabetes is a known risk factor for COVID-19, researchers with Brigham and Women's Hospital have identified a rare COVID-19 complication with common diabetes drugs. The side effect is called euDKA, or euglycemic diabetic ketoacidosis. DKA occurs when the bodys cells do not absorb enough glucose and begin metabolizing fats instead, which results in a build-up of ketones. EuDKA is marked by lower blood sugar levels, making it harder to diagnose. The researchers evaluated five unusual euDKA cases that was a significantly higher level of incidence, all seen in COVID-19 patients taking sodium-glucose cotransporter 2 inhibitors (SLGLT2i). They believe that COVID-19 may increase the risk of euDKA by binding to cells on the pancreas that produce insulin. The three SGLT2 inhibitors approved by the FDA are Janssens Invokana (canagliflozin), AstraZenecas Farxiga (dapagliflozin) and Eli Lilly and Boehringer Ingelheims Jardiance (empagliflozin).

Whats Going on in the International Space Station?

The Expedition 64 crew took the day off for Christmas, but immediately afterwards went back to work on a variety of biological and medical research. Two studies evaluated new treatments for joint injuries and cancerone looked at bone, cartilage and synovium in artificial gravity chambers to better understand bone loss and joint damage; the second studied protein crystals grown in space and their ability to target cancer cells. A different study on several dozen mice evaluated the vascular changes in space on eyesight functionabout 40% of people working in space have vision changes from fluid shifts and radiation. Another experiment studied genetic changes in space and their impact on the growth and deterioration of bone tissue.

See the article here:
Research Roundup: Different Antibody Responses to COVID-19 and More - BioSpace

People wear face masks as they walk by an art installation in Montreal, Dec. 27, 2020, as the COVID-19 pandemic continues in Canada and around the world.

Graham Hughes/The Canadian Press

The emergence of a more contagious variant of the virus that causes COVID-19 does not require individuals to take new precautions, but it is now more important than ever that they follow existing public-health guidelines, doctors and scientists say.

While new variants of the virus SARS-CoV-2 have recently been detected in South Africa, Nigeria and Britain, the latter countrys version, called B117, has caused particular concern, as scientists estimate it is more transmissible than other mutations of the virus. This new variant has also been identified in people in Ontario, British Columbia, Alberta and Quebec, and the Canadian government has suspended flights from Britain until Jan. 6. Meanwhile in Britain, there are growing calls to impose another national lockdown and shut down schools and universities.

In a study, yet to be peer-reviewed, British scientists estimated B117 is 56 per cent more transmissible than pre-existing variants of the virus. Although they found no clear evidence that it affects the severity of illness, they warned that the increased transmissibility would likely lead to a surge in hospital admissions and deaths. They suggested strict lockdown measures may not be sufficient, unless primary schools, secondary schools and universities are closed.

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I would say that the current social distancing guidelines are more important than ever given this new variant, lead author Nicholas Davies of the London School of Hygiene and Tropical Medicine said in an e-mail. People should be cautious, follow the guidelines, and self-isolate if they suspect they may have been infected.

But the estimated increased transmissibility of the new variant does not mean existing public-health advice for personal protection such as wearing masks when you may come in close contact with others, keeping two metres away from people outside your household and maintaining hand hygiene will be less effective, experts say.

Rather than changing the current guidelines, Leighanne Parkes, an infectious-disease specialist and microbiologist at the Jewish General Hospital in Montreal, said she would be happy to see people actually follow them.

People take little shortcuts from time to time and give themselves little cheat days. And I think thats where the danger lies, when we let down our guard and we fail to remain vigilant, she said.

Dr. Parkes said family members have contacted her over the holidays, expressing worry that this new variant adds another twist to an already calamitous year. But, she explained, there have been numerous variants since the very emergence of SARS-CoV-2. And some, such as a variant called D614G, have become predominant worldwide.

Dr. Parkes said it is important to note that large task forces and working groups at the global level are trying to determine the significance of the changes to the virus in the new variant.

Technically, she said, it involves a mutation within a part of the binding loop, which is part of the virus that sticks to our ACE-2 receptors, the part of the cell to which the virus binds to gain entry. The concern is that since this mutation affects an important part of the virus and how it attaches to cells, it raises questions such as whether it has increased tissue-specificity that is, it binds to cells in the nose and upper respiratory tract where it can be spread through droplets with greater ease, whether smaller quantities of the virus can lead to infection, and whether it changes the way people respond to it.

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While there are experts working to rapidly answer these questions, I think as of now, we just dont know. These are all kind of black holes in our knowledge, she said.

In an e-mailed statement, Health Canada said the government is closely monitoring the variant and is working with international groups, including the World Health Organization.

While early data suggest that the United Kingdom variant may be more transmissible, to date there is no evidence that the mutations have any impact on symptom severity, antibody response or vaccine efficacy, it said, but noted evidence is limited at this time.

But no matter the variant, SARS-CoV-2 is a virus that transmits very easily, and it is well known that people can spread it when they are minimally symptomatic or asymptomatic, Dr. Parkes said.

As always, given the high potential for asymptomatic transmission of SARS-CoV-2, the most prudent course of action for individuals is to act as though they might have the virus, Dr. Davies at the London school added in his e-mail.

While the mutations of the new variant may change how efficiently people contract the virus, they do not change the mechanism by which it spreads, said Emanuel Goldman, a virologist and professor of microbiology, biochemistry and molecular genetics at Rutgers New Jersey Medical School.

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The main route of transmission is still through what we breathe, so wearing a mask in public places, particularly indoors, is still the first line of defence, Dr. Goldman said. There is no need to go back to wiping down groceries as many did at the beginning of the pandemic, since transmission of the virus from surfaces is almost non-existent, he said.

The virus may be more transmissible, but its not less fragile, he said, explaining it degrades rapidly when exposed to the environment.

When it comes to behaviours that stop the virus, everything should stay the same. What works for the parent will work for the variants, Dr. Goldman said.

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Experts stress importance of following public-health advice as COVID-19 variant emerges - The Globe and Mail

The great but grumpy biologist J.B.S. Haldane was once asked what evidence would disprove evolution, whereupon he growled: Fossil rabbits in the Precambrian. He was referring to the evolutionary fact that complex multicellular creatures came along later than simple, unicellular ones. A bit surprising, perhaps, that one of the foremost evolutionary geneticists of the 20th century immediately reached for a paleontological example, but Haldanes reply was well-suited for public consumption, because thenas nowwhen most people thought of evolution, they were likely to conjure images of dinosaur fossils.

Donald Prothero is a research associate in vertebrate paleontology at the Natural History Museum of Los Angeles County. When I learned he had written a book that examined 25 different discoveries relating to evolution, I assumed that he, like Haldane, would deploy paleontology in making his case. Mr. Protheros book is indeed tilted toward examples from the world of ancestral creatures, but, refreshingly, also guides the reader through impressive discoveries in embryology and molecular genetics.

The Story of Evolution in 25 Discoveries is a parade of self-contained vignettes, often including biographical sketches of the scientists who made and interpreted each discovery. This particular story begins (like everything else) with the big bang, followed by the fascinating tale of how science gradually came to understand the age of the Earth: From biblical literalism; through Lord Kelvins famous underestimate, in the 1890s, of 20 million years; to our current understanding of 4.5 billion years. Then comes a whirlwind tour of evolutionary change as it occurs, in real time, among microbes, plants, insects, fish, birds and mammals, obliterating the creationist canard that evolution hasnt even been witnessed, let alone studied.

Some of the most impressive evolutionary stories involve common body plans, technically known as homologies. Thanks to Mr. Prothero, I now know that Aristotle first noticed this widespread phenomenon, of which Darwin wrote: What can be more curious than that the hand of a man, formed for grasping, that of a mole for digging, the leg of the horse, the paddle of the porpoise, and the wing of the bat, should all be constructed on the same pattern, and should include similar bones, in the same relative positions? Curious indeed. And strongly suggestive of common descentor, for anti-evolutionists, of a Creators insistence on sticking with the same divine blueprint, or archetype, even when other more direct routes should have been available. The Darwinian story provides scientific insight into why homologies occur, whereas the theological story simply reiterates that they occur.

And on we go, to the embryonic similarities of otherwise distantly related creatures (ontogeny recapitulates phylogeny) and then biogeography (the sinking of Noahs Ark), which shows, among other relevant findings, that the flora and fauna of islands resemble those of nearby continentsa phenomenon that wouldnt necessarily be expected if each had been a special, independent creation. The story of life continues, detailing how living things within natural categories share those common body plans, or, as Darwin put it, how organic beings have been found to resemble each other in descending degrees, so that they can be classed in groups under groups. As a result, instead of being arbitrary, our system of biological classification conforms perfectly with the nested, branching patterns of evolutionary relationships demonstrated by anatomy, physiology and genetics. Moreover, as Mr. Prothero points out, if life had been specially created rather than evolved, there would be no reason for the molecular systems to reflect this pattern of similarity seen in megascopic features . . . [and] not even Darwin could have dreamed that the genetic code of every cell in your body also shows the evidence of evolution.

Originally posted here:
The Story of Evolution in 25 Discoveries Review: The Branching Tree of Life - The Wall Street Journal

BY THOMAS J ERVIN, MD We have somehow made it to the final week of 2020. Humorously it can be said that we can all look back at the first year of the pandemic, with usually accurate 20/20 vision. As we all move into 2021, there is time to consider New Years resolutions. This year that opportunity should not go unfilled.

The effects of COVID-19 have spared no one. Even the most skeptical of us, and the unbelievers have noticed something. The negatives are obvious: illness, personal loss, death, social distancing, and isolation to name a few. Positives can also be identified, including personal faith, strengthening family relationships, considering collective wellbeing, and finding value in simple daily routines.

For each of us the balance of the positives and the negatives results in how we see the pandemic and the events of 2020. This balance determines how we consider resolutions for the future. As I am not a student of politics and race relations, I will avoid those events in my reflection of 2020.

My first resolution for 2021 is that this will be the last article I write about COVID-19 and the pandemic. I have spent 40 years teaching, studying, and practicing medicine. I have seen the impact of molecular genetics and biology in most specialties including cancer medicine and infectious diseases. To witness the development of the applied science that has given us potentially preventative vaccines (now there are at least four) within a year is both astounding and unprecedented.

Just 65 years ago injectable inactivated polio vaccine (Dr. Salk) became a reality. It then took six more years for the oral vaccine (Dr. Sabin) to be commercially developed. The overall research effort took more than 20 years. Two doses given four to eight weeks apart provide life-long immunity. Yet eradication of the disease was not immediate.

While the United States is considered polio-free, it has taken until 2017 for the number of wild-type polio cases in the world to fall under 1,000 cases a year. Over the past 30 years, things have gotten better. With continued development of effective vaccine platforms and better understanding of the variables that affect vaccine efficiency (number of doses, added immunostimulants, immunosenescence with age), the vaccines of the 21st century have been more rapidly developed. Successful vaccines are now possible using inactivated intact virus, attenuated virus, toxoids that induce illness such as tetanus, and diphtheria, or subunit viral pieces as in the vaccines for Hepatitis B and Herpes virus. Other forms of vaccines exist, including conjugate vaccine and heterotypic vaccines such as BCG used to prevent tuberculosis and bladder cancer. The list grows yearly.

Now we have the first of a new wave of vaccines. The mRNA platform has arrived just in time. The mRNA-based vaccines being offered by Pfizer-NBiotech and by Moderna have been produced in record time. They come as a result of a decade of research developing innovative vaccines attempting to stimulate an immunologic response to both cancers and emerging viral threats such as Ebola. Synthetic production of mRNA nucleotide fragments and synthetic nanoparticle delivery envelopes have made possible the rapid development of the safe and effective vaccines now available to prevent coronavirus infection and COVID-19 illness. Similarly, the vaccines being developed by AstraZeneca, Novavax and Johnson & Johnson will quickly add options for effective vaccination for us all.

I say BRING IT ON!!!

Yet, in closing 2020, I think back on the history of vaccine development. Without comprehensive programs that incorporate the basics of public health, vaccination programs can work only so well or so fast. Surely, the rollout of the available vaccines will occur. The Boca Grande Health Clinic is in line with four separate pipelines for distribution. Unfortunately, the process is still too early for us to be able to identify the exact sources and timeline of delivery.

It is very likely that we will all have an opportunity for vaccination before the summer, but the next 90 to 180 days (not six to 20 years as in the past) will be critical for many of us. Unless we all buy into doing the right things collectively, COVID-19 will continue among us.

As my last words on COVID-19 (I promise), please wash your hands. Please wear a mask, especially indoors. And please distance yourself and avoid unnecessary indoor gatherings. Before Jenner figured out how to prevent smallpox just before 1800, one of every 13 persons living in London died or was severely disfigured by the disease. Be delighted you are living in 2021, at a time when science and public health policy can help you live well if you listen.

Have a happy and healthy 2021.

Thomas J. Ervin, M.D.

Boca Grande Health Clinic

Marcy Shortuse is the editor of the Boca Beacon, and has been with the paper since 2007. She is also editor of the Boca Beacon's sister publication, Gasparilla Magazine.She has more than 20 years of experience writing and editing local newspapers and is originally from the Chicago area.

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New Year's resolution 2021: A (last) word from Dr. Ervin - Boca Beacon

A study conducted by the World Health Organisation (WHO) estimated that 5.2 million children under five years of age died mostly from preventable and treatable causes in 2019. This staggering number can be brought down if advanced technology meets medicine to develop an early warning system.

This is the path taken by CognitiveCare, a healthtech startup founded by Venkata Narasimham Peri and Dr Suresh Attili and based out of Hyderabad and California, US.

Venkata Narasimham Peri, popularly known as PV, was a technology business consultant for more than two decades, having worked with PwC and other organisations. He decided to become an entrepreneur at the age of 48 when he realised artificial intelligence (AI) could become a valuable tool for the healthcare industry.

PV partnered with Dr Suresh Attili, a leading oncologist and scientist, to start CognitiveCare in 2018. The duo toyed with various segments like mental health and cancer, but decided to focus on maternal and infant healthcare, given the enormity of the problem.

He adds that the world loses 800 women to pregnancy-related complications every day and millions go through very complex pregnancies.

Both the founders bootstrapped CognitiveCare with an investment of $300,000 and decided to build an AI technology platform that could provide all relevant health indicators of an expectant mother to her doctor.

This AI platform, Maternal Infant Health Insights and Cognitive Intelligence (MIHIC), is a neural network that analyses all data of an expectant mother and come out with a score.

The development of such an open-sourced AI computing model also required an interdisciplinary approach as it was not just about medicine or computing algorithms. It also delved into other subjects such as mathematics, statistics,genetics, and even sociology.

The CognitiveCare team is inter-disciplinary and includes research scientists with a mathematics background and others with a focus on molecular genetics and software codes.

CognitiveCare founders: Dr Suresh VS Attili (left) and Venkata Narasimham Peri

Risk assessment

The MIHIC platform analyses all medical, clinical, genetic, radiological, social, and lifestyle determinants to predict early signs of maternal, infant, and foetal risks.

In short, MIHIC provides scores on all 48 indicators. For example, PV says, their studies have shown that women who stay near the sea have a higher probability of developing folic acid deficiency.

The score we provide allows for early-risk detection so doctors can take preventive action, PV says. He clarifies that the job of CognitiveCare is to only provide indicators; the decision on the treatments is the doctors alone.

CognitiveCare has taken all mandatory approvals and is HIPAA-compliant; it meets the highest standards in terms of maintaining privacy of the patients identity and data.

The healthtech startup has been in stealth mode till now and its technology platform has evinced interest from leading medical schools and institutions in United States and India. For example, Brigham and Womens Hospital in Boston, Massachusetts, is directing the research study to test MIHIC.

PV believes the application and benefits of their technology platform are not restricted to just hospitals as others like the government, pharmaceutical companies, and even health insurance firms stand to gain.

It can also accelerate the drug discovery process for pharmaceutical companies with better insights on maternal and infant care. Insurance companies can assess risks more accurately by using this platform.

CognitiveCare will primarily look at markets in the US, the UK, and India.

PV says many medical institutes are willing to share data, and feels the healthtech startup has no direct competition as it provides a 360-degree view of womens maternal health.

The founder says CognitiveCare's focus for the next three to four years would be maternal and infant healthcare. The startup, which has already $900,000 in a seed round with a pre-money valuation of $8 million, says they will later explore other areas of health.

We not only want to empower the doctor, but our eventual goal is that every woman - not just an expectant mother - can gauge her obstetric health," PV says.

More:
This healthtech startup uses AI to assess health risks of expectant mothers - YourStory

The lowest part of a childs brain is visible below the bottom of the skull in this MRI scan and shows evidence of a Chiari 1 malformation. Researchers at Washington University School of Medicine in St. Louis have shown that Chiari 1 malformation can be caused by variations in two genes linked to brain development, and that children with large heads are at increased risk of developing the condition. Credit: David Limbrick

Discovery could aid early screening, shed light on how Chiari malformation arises.

About one in 100 children has a common brain disorder called Chiari 1 malformation, but most of the time such children grow up normally and no one suspects a problem. But in about one in 10 of those children, the condition causes headaches, neck pain, hearing, vision and balance disturbances, or other neurological symptoms.

In some cases, the disorder may run in families, but scientists have understood little about the genetic alterations that contribute to the condition. In new research, scientists at Washington University School of Medicine in St. Louis have shown that Chiari 1 malformation can be caused by variations in two genes involved in brain development.

The condition occurs when the lowest parts of the brain are found below the base of the skull. The study also revealed that children with unusually large heads are four times more likely to be diagnosed with Chiari 1 malformation than their peers with normal head circumference.

The findings, published Dec. 21 in the American Journal of Human Genetics, could lead to new ways to identify people at risk of developing Chiari 1 malformation before the most serious symptoms arise. It also sheds light on the development of the common but poorly understood condition.

A lot of times people have recurrent headaches, but they dont realize a Chiari malformation is the cause of their headaches, said senior author Gabriel Haller, PhD, an assistant professor of neurosurgery, of neurology and of genetics. And even if they do, not everyone is willing to have brain surgery to fix it. We need better treatments, and the first step to better treatments is a better understanding of the underlying causes.

If people start experiencing severe symptoms like chronic headaches, pain, abnormal sensations or loss of sensation, or weakness, the malformation is treated with surgery to decompress the Chiari malformation.

Theres an increased risk for Chiari malformations within families, which suggests a genetic underpinning, but nobody had really identified a causal gene, Haller said. We were able to identify two causal genes, and we also discovered that people with Chiari have larger head circumference than expected. Its a significant factor, and easy to measure. If you have a child with an enlarged head, it might be worth checking with your pediatrician.

To identify genes that cause Chiari 1 malformation, Haller and colleagues sequenced all the genes of 668 people with the condition, as well as 232 of their relatives. Of these relatives, 76 also had Chiari 1 malformation and 156 were unaffected. The research team included first author Brooke Sadler, PhD, an instructor in pediatrics, and co-authors David D. Limbrick, Jr., MD, PhD, a professor of neurosurgery and director of the Division of Pediatric Neurosurgery, and Christina Gurnett, MD, PhD, a professor of neurologyand director of the Division of Pediatric and Developmental Neurology, among others.

Sequencing revealed that people with Chiari 1 malformation were significantly more likely to carry mutations in a family of genes known as chromodomain genes. Several of the mutations were de novo, meaning the mutation had occurred in the affected person during fetal development and was not present in his or her relatives. In particular, the chromodomain genes CHD3 and CHD8 included numerous variants associated with the malformation.

Further experiments in tiny, transparent zebrafish showed that the gene CHD8 is involved in regulating brain size. When the researchers inactivated one copy of the fishs chd8 gene, the animals developed unusually large brains, with no change in their overall body size.

Chromodomain genes help control access to long stretches of DNA, thereby regulating expression of whole sets of genes. Since appropriate gene expression is crucial for normal brain development, variations in chromodomain genes have been linked to neurodevelopmental conditions such as autism spectrum disorders, developmental delays, and unusually large or small heads.

Its not well known how chromodomain genes function since they have such a wide scope of activity and they are affecting so many things at once, Haller said. But they are very intriguing candidates for molecular studies, to understand how specific mutations lead to autism or developmental delay or, as in many of our Chiari patients, just to increased brain size without cognitive or intellectual symptoms. Wed like to figure out the effects of each of these mutations so that in the future, if we know a child has a specific mutation, well be able to predict whether that variant is going to have a harmful effect and what kind.

The association between chromodomain genes and head size inspired Haller and colleagues to measure the heads of children with Chiari malformations, comparing them to age-matched controls and to population averages provided by the Centers for Disease Control and Prevention. Children with Chiari tended to have larger than average heads. Those children with the largest heads bigger than 95% of children of the same age were four times more likely to be diagnosed with the malformation.

The findings suggest that children with larger heads or people with other neurodevelopmental disorders linked to chromodomain genes may benefit from screening for Chiari malformation.

A lot of kids that have autism or developmental disorders associated with chromodomain genes may have undiscovered Chiari malformations, Haller said. The only treatment right now is surgery. Discovering the condition early would allow us to watch, knowing the potential for serious symptoms is there, and perform that surgery as soon as its necessary.

Reference: Rare and de novo coding variants in chromodomain genes in Chiari I malformation by Brooke Sadler, Jackson Wilborn, Lilian Antunes, Timothy Kuensting, Andrew T. Hale, Stephen R. Gannon, Kevin McCall, Carlos Cruchaga, Matthew Harms, Norine Voisin, Alexandre Reymond, Gerarda Cappuccio, Nicola Burnetti-Pierri, Marco Tartaglia, Marcello Niceta, Chiara Leoni, Giuseppe Zampino, Allison Ashley-Koch, Aintzane Urbizu, Melanie E. Garrett, Karen Soldano, Alfons Macaya, Donald Conrad, Jennifer Strahle, Matthew B. Dobbs, Tychele N. Turner, Chevis N. Shannon, Douglas Brockmeyer, David D. Limbrick, Christina A. Gurnett and Gabe Haller, 21 December 2020, American Journal of Human Genetics.DOI: 10.1016/j.ajhg.2020.12.001

This study was funded by Sam and Betsy Reeves and the Park-Reeves Syringomyelia Research Consortium; the University of Missouri Spinal Cord Injury Research Program; the Childrens Discovery Institute of St. Louis Childrens Hospital and Washington University; the Washington University Institute of Clinical and Translational Sciences, grant number UL1TR000448 from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH); the Eunice Kennedy Shriver National Institute of Child Health & Human Development, award number U54HD087011 to the Intellectual and Developmental Disabilities Research Center at Washington University; the Swiss National Science Foundation, grant number 31003A_182632; and the Jrme Lejeune Foundation.

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Common Brain Malformation Affecting About 1 in 100 Children Traced to Its Genetic Roots - SciTechDaily

The genetic cause of a common brain malformation has been traced to variations in two genes associated with brain development, according to researchers atWashington University in St. Louis (WUSTL). This news, published in the American Journal of Human Genetics, enables researchers to develop early screening methods before the most serious symptoms arise, and thus intervene.

Chiari 1 malformation is a common, yet poorly understood condition. It is present in about 1% of children and occurs when the cerebellum is displaced through the foramen magnum into the spinal canal, thus placing part of the brain below the base of skull.

Usually, the condition is harmless, causing no or only minor medical issues. In 10% of those children, however, Chiari 1 malformation causes problems severe headaches, neck pain, and issues with hearing, vision, and balance or other neurological manifestations.

Gabriel Haller, Ph.D., an assistant professor of neurosurgery, neurology and of genetics, and his colleagues conducted whole-exome sequencing on 668 children diagnosed with Chiari 1 malformation. It revealed significant enrichment of variants in the chromodomain genes. They found, specifically, a significant burden of rare, transmitted variants in CHD3 and three loss of function variants in CHD8. Many of these variations were de novo, occurring during fetal development and not among family members.

The researchers also found that children with Chiari 1 who had larger heads (compared to age-matched controls and to population averages provided by the Centers for Disease Control and Prevention) often had CHD variants. Specifically, those whose heads were larger than 95% of children of the same age were four times more likely to be diagnosed with the malformation.

Its a significant factor, and easy to measure. If you have a child with an enlarged head, it might be worth checking with your pediatrician, Haller, senior author of the paper, said in a statement.

For severe symptoms, the Mayo Clinic says surgery is the most common treatment. Its goal is to to reduce the pressure on the brain and to halt further anatomic changes to the brain and spinal canal. Surgery may involve removing bone at the base of the skull, opening the dura mater covering the brain, or removing part of the spinal column to provide more room for the brain or spinal cord.

A lot of times people have recurrent headaches, but they dont realize a Chiari malformation is the cause of their headaches, Haller said. And even if they do, not everyone is willing to have brain surgery to fix it. We need better treatments, and the first step to better treatments is a better understanding of the underlying causes.

Theres an increased risk for Chiari malformations within families, which suggests a genetic underpinning, but nobody had really identified a causal gene, Haller said. Of the 232 family members who also underwent gene sequencing, 76 also had Chiari 1 malformation and 156 were unaffected.

The involvement of the CHD8 gene in regulating brain size was confirmed, in further experiments, on transparent zebrafish. When the researchers inactivated one copy of the fishschd8gene, the animals developed unusually large brains, with no change in their overall body size.

The implications of the finding extend beyond Chiari 1 malformations. Chromodomain genes are involved in regulating multiple sets of genes. As such, they also play a role in a variety of neurodevelopmental conditions, such as autism and developmental delays.

Its not well known how chromodomain genes function, since they have such a wide scope of activity and affect so many things at once, Haller said. But they are very intriguing candidates for molecular studies, to understand how specific mutations lead to autism or developmental delay or, as in many of our Chiari patients, just to increased brain size without cognitive or intellectual symptoms.

Wed like to figure out the effects of each of these mutations so that in the future, if we know a child has a specific mutation, well be able to predict whether that variant is going to have a harmful effect and what kind.

More than 20 clinical trials are underway for this condition, according to ClinicalTrials.gov. Most involve surgical procedures, although a few involve diagnostics. The trial most relevant to drug developers may be a genetics study of 1,000 patients completed by researchers at Duke University in 2017.

While not definitive, it implicated the COL5A2, COL7A1, COL1A2 genes, associated with Ehlers-Danlos syndrome, epidermolysis bullosa, and other conditions; and NRP1, FLT1, VEGFA and VEGFB genes because of their roles in the growth signaling pathway and in placental and vascular development. It confirmed the role of genetics in Chiari malformations and implicated linkages to variations in 21 genes.

Data from a December 2020 study is still being analyzed by the National Institute of Neurological Disorders and Stroke to analyze genetic linkages.

A lot of kids that have autism or developmental disorders associated with chromodomain genes may have undiscovered Chiari malformations, Haller said. The only treatment right now is surgery. Discovering the condition early would allow us to watch, knowing the potential for serious symptoms is there, and perform that surgery as soon as its necessary.

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WUSTL Researchers ID Elusive Cause of Chiari 1 Brain Malformation - BioSpace

The Oxford team is led by Sarah Gilbert, professor of vaccinology at the universitys Jenner institute. She has hailed thefirst authorisation of use of the vaccine outside clinical trialsas aday for the team developing the vaccine to celebrate, after a year of extremely hard work under difficult circumstances. Although in the same sentence she struck a typically cautionary note: We still have more to do

Even after their vaccine has become just the third in the world to be granted regulatory approval (following the Pfizer/BioNTech and Moderna vaccines), nobody could accuse the Oxford researchers of being swept away in the hype. Indeed Gilbert and others in her team have spoken openly about how little they have enjoyed the constant attention over the past year, preferring instead to focus on their life-saving work.

During that time, lucrative offers for after dinner speaking gigs have started to roll in for Gilbert, which she has rejected in turn. Another key member of the Oxford group, Professor Catherine Green, who heads the universitys clinical biomanufacturing facility, recently described the media attention as awful. Of their new-found fame, she added: Its not something that we got into our careers to do.

The motivations of the Oxford team can instead be neatly surmised by a mug that Gilbert keeps in her office at the Jenner Institute, which says: Keep calm and develop vaccines. It is a mantra that has served her and her colleagues well this year, juggling the exhaustion of constant work with family life.Gilbert, after all, is the mother of 21-year-old triplets (biochemistry students at Oxford and Bath Universities) who took part in the phase 1 clinical trials of the vaccine. Her regime has involved getting up at about 4am each day, cycling to the laboratory and returning home at about 8pm.

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'Keep calm and develop vaccines': Meet the scientists behind the Oxford jab - Telegraph.co.uk

The latest market intelligence study on Nucleic Acid-based Therapeutics Market relies on the statistics derived from both primary and secondary research

Nucleic Acid-Based Therapeutics are used to target genes responsible for either the expression of a disease causing proteins or to correct the decreased protein expression in diseases where the absence of the protein contributes to a disease state. The Global Nucleic Acid-Based Therapeutics Market is expected to reach around USD 741.98 million by the end of the forecast period and is expected to grow at a CAGR of ~6.8%.

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https://celinaredden1645.wixsite.com/healthcaretrending/post/nucleic-acid-based-therapeutics-market-top-companies-analysis-upcoming-trends-emerging-growth

Nucleic acid-based therapeutics are target deficiencies or dysfunctions at the molecular level and are targeted therapies. These are used specifically to target genetic diseases and disorders for which there exists no permanent cure such as thalassemia, sickle cell anemia, hemophilia, cystic fibrosis, diabetes etc. The nucleic acid-based therapeutics are based on accurate target identification and genetic profiling and the human gene project has formed the backbone of these class of drugs. As such nucleic acid-based medication have one of the most versatile and revolutionary potential.

The critical market driver for nucleic acid-based therapies is the poor cure rates for genetic diseases with traditional drugs. Other market drivers include increasing understanding of the human genetics, growing capabilities of mapping human tissue molecular targets, rising power of softwares to mimic the human molecular entities such as receptors etc.

Global Nucleic Acid-Based Therapeutics Market Study Objectives

To provide detail analysis of the market structure along with forecast for the next 6 years of the various segments and sub-segments of the global nucleic acid-based therapeutics market To provide insights about factors affecting the market growth To analyze the market based on various factors- price analysis, supply chain analysis, porters five force analysis etc. To provide historical and forecast revenue of the market segments and sub-segments with respect to four main geographies and their countries- Americas, Europe, Asia-Pacific, and Middle East & Africa.

Global Nucleic Acid-based Therapeutics Market Key Players

Some of the key players in this market are: Wave Life Sciences Ltd., Copernicus Therapeutics Inc., Imugene, Caperna, Phylogica, Protagonist Therapeutics, Benitec Biopharma, EGEN (Expression Genetics), Benitec Biopharma, BioMedica (Oxford BioMedica), Transgeneand others.

Global Nucleic Acid-based Therapeutics Market Regional Analysis

Globally America is the largest market for nucleic acid-based therapeutics. The presence of strong research base, excellent reimbursement scenario, the good provisions for orphan diseases and drugs and the rapid uptake of new drugs and technology are the prime reasons for this dominance. Europe is the second-largest market for nucleic acid-based therapeutics. The developed markets are likely to maintain their leads due to the nonexistence of regulatory framework in the developing and poor regions of the world such as Asia pacific region and Africa.

Global Nucleic Acid-based Therapeutics Market Intended Audience

Nucleic Acid-based Therapeutics Manufacturers

Nucleic Acid- based Therapeutics Suppliers

Private Research Laboratories

Research and Development (R&D) Companies

Market Research and Consulting Service Providers

Government Research Laboratories

Contract Manufacturing Organizations

Global Nucleic Acid-based Therapeutics Market Segments

Global nucleic acid-based therapeutics market has been segmented on the basis of technology which comprises anti-sense and anti-gene, short inhibitory sequences, gene transfer therapy, nucleoside analogs, ribozymes, aptamers and others. On the basis of applications; market is segmented into monogenetic disorders which is further sub segmented into thalassemia, sickle cell anemia, hemophilia, cystic fibrosis etc. and multi-genetic disorders which is sub segmented into cancer, diabetes, neurodegenerative diseases, cardiovascular diseases etc. On the basis of end users; market is segmented into hospitals, academic & research institutes.

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UCLA has received a $7.3 million grant from the National Institutes of Health to build a state-of-the-art facility in which to produce gene and cell therapies aimed at treating a host of illnesses and conditions.

The new 13,000-square-foot facility, to be constructed in UCLAs Center for the Health Sciences, will provide a highly regulated environment with features such as systems to manage air flow and filtering, laboratory spaces and bioreactors. The new facility is expected to be ready for use in 2023.

This grant provides critical funds to build a facility that will enable the development of a new generation of cellular therapies for cancer and other deadly diseases, said Dr. AntoniRibas, a UCLA professor of medicine and director of the Parker Institute for Cancer Immunotherapy Center at UCLA.

The new facility will be built according to U.S. Food and Drug Administrationgood manufacturing practices, a set of guidelines intended to ensure that facilities producing products for human use are built to maximize safety and effectiveness, and to reduce the risk for contamination.

It will replace a facility in UCLAs Factor Building that UCLA scientists currently use for similar research. But that space, which was put together by combining existing research laboratories, lacks the capacity to process certain cells and handle other bioengineered products, and it cannot accommodate the growing number of UCLA scientists pursuing research on gene and cell therapies, said Dr. Stephen Smale, vice dean for research at the David Geffen School of Medicine at UCLA and principal investigator of the NIH grant.

The new facility will be larger, so it will be able to support more projects simultaneously, and its design will allow a smooth flow of products into and out of the facility, Smale said. The larger number of rooms is really important because even when a single therapy is being tested, cells from each patient need to be processed in their own room.

Dr. Eric Esrailian, chief of theUCLA Vatche and Tamar Manoukian Division of Digestive Diseases, is helping to lead the expansion of UCLAs immunology and immunotherapy efforts. It will be a cornerstone for UCLAs commitments to building on existing strengths in the areas of immunology and immunotherapy and expanding toward the creation of a transformational institute in these fields, he said.

Despite the shortcomings of the current space, UCLA researchers have still produced groundbreaking work in it. These include tumor-targeting therapies developed by Ribas, Dr. Donald Kohn, Dr. Linda Liau, and other UCLA researchers.

Ribas, Kohn and Liau are also members of theUCLA Jonsson Comprehensive Cancer Centerand theUCLA Broad Stem Cell Research Center. Kohn is a distinguished professor of microbiology, immunology and molecular genetics and Liau is chair of UCLAs department of neurosurgery.

Kohn, who alsodeveloped a cure for bubble baby syndrome,said he will welcome the new facility because of its increased capacity for researchers to pursue treatments and cures that could significantly improve the health and quality of life of so many people. For instance, it will have the capacity to produce large batches of viral vectors microbes that make it possible to introduce potentially curative genes into cells for gene therapy studies.

This new facility will allow the innovative cell and gene therapies pioneered at UCLA to be available to a wider number of patients and accelerate the development of novel cures, said Kohn, whose work has also led to an experimental stem cell gene therapy for sickle cell disease that is showing promising early results in clinical trials.

Liau, a neuro-oncologist, said the new facility will enable researchers to create personalized vaccines and cell therapies for a much larger number of patients.

In the current facility, we are only able to enroll one patient at a time in our cell therapy trials, so many eligible patients have had to be turned away, Liau said.With greater capacity to manufacture gene and cell therapy products that meet FDA good manufacturing practice standards, this new UCLA facility will really allow us to further innovate and accelerate our translational research toward a cure for brain cancer.

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UCLA receives $7.3 million grant to build state-of-the-art facility for developing gene, cell therapies - UCLA Newsroom

UNM researchers discover certain materials combined with UV light can kill coronavirus and other viruses

As the deadly COVID-19 pandemic continues to wreak havoc around the world with no end in sight, new ways in which to stop the spread or mitigate the effects of the disease are few.

Although most experts agree that a vaccine would significantly slow or eventually stop the spread, the work to develop, approve and distribute such a vaccine are likely months away. That leaves us with only prevention efforts such as masks, social distancing and disinfecting, which partially due to human inconsistencies in behavior, have proven to be variable in effectiveness.

Despite these grim realities about the novel coronavirus that has taken 2020 by storm, disrupting the work, school and personal lives of nearly everyone on the globe, some University of New Mexico researchers have found a possible breakthrough in how to manage this virus, as well as future ones.

A team led by the Center for Biomedical Engineering faculty David Whitten, Distinguished Professor in the Department of Chemical and Biological Engineering, along with Eva Chi and Linnea Ista, faculty members in the same department, have found some light at the end of the tunnel, so to speak.

The main finding of their research, highlighted in the paper, Highly Effective Inactivation of SARS-CoV-2 by Conjugated Polymers and Oligomers, published this week in the journal ACS Applied Materials & Interfaces, involves the ability of the combination of certain polymers and oligomers, when combined with UV light, to almost completely kill the coronavirus.

UNM co-authors on the paper were Florencia A. Monge, of UNMs Center for Biomedical Engineering and the biomedical engineering graduate program; Virginie Bondu of the Department of Molecular Genetics and Microbiology at the UNM School of Medicine; Alison M. Kell, Department of Molecular Genetics and Microbiology at the UNM School of Medicine; and Patrick L. Donabedian of the nanoscience and microsystems engineering graduate program at UNM. Also on the team are Kirk S. Schanze and Pradeepkumar Jagadesan, both of the Department of Chemistry at the University of Texas at San Antonio.

Although disinfectants such as bleach or alcohol are effective against the virus, they are volatile and corrosive, which limit lasting sterilization of surfaces treated by these products, Whitten said.

What is different about these polymer and oligomer materials is that when activated with UV light, they provide a coating that is shown to be fast acting and highly effective, reducing the concentration of the virus by five orders of magnitude, Chi said.

These materials have shown to have broad-spectrum antiviral properties, she said.

Whitten points out that in order for the material to be active against the virus, it must be exposed to light. Light activates the docking process that is important and necessary for placing the oligomer or polymer at the surface of the virus particle, allowing the absorption of light that generates the reactive oxygen intermediate at the surface of the virus particle.

As far as we know so far, materials such as ours are not active against SARS-CoV-2 in the dark and require activation by irradiation with ultraviolet or visible light, depending on where the specific antimicrobial absorbs light, he said. In the dark, our antimicrobial materials dock with the virus, and then on irradiation, they activate oxygen. It is this active, excited state of oxygen that starts the chain of reactions that inactivate the virus.

And this science can easily be applied into consumer, commercial and healthcare products, such as wipes, sprays, clothing, paint, personal protective equipment (PPE) for healthcare workers, and really almost any surface.

When incorporated into N95 masks, this material works well against the virus, Chi said. In addition to trapping the virus in a mask, this would make for better PPE and prolong its life.

Another unique advantage of this material is that unlike traditional disinfectant products, it is shown to not wash away with water and leaves no toxic residue as a result of the photodegradation process, Chi said.

Studying the potential of conjugated polymers and oligomers is nothing new for UNM researchers. In fact, Whitten and another of the authors on the study, Kirk Schanze, have been researching this area for a couple of decades.

Whitten and Chi said colleagues such as Schanze and others have collected a lot of data on polymer and oligomers, so when the pandemic hit in the spring, Whitten almost immediately started wondering how his area of study could help.

It was the right timing for all of us, Chi said.

Acquiring live coronavirus for research is not an easy feat, but thanks to the efforts a couple of team members, they were able to make it happen.

Linnea Ista is a member of the Biosafety Committee at UNM, and when the pandemic broke out and she was aware of the research that Whitten and Chi were conducting, she realized that she may have a connection on how to make the research happen, due to the fact that representatives from UNMs School of Medicine also sit on the committee.

Alison Kell, a faculty member in the School of Medicine, was the one who was able to acquire the live coronavirus for testing the effectiveness of these materials. She has been working with the SARS-CoV-2 virus in her research and was able to develop a protocol for analyzing samples the team prepared and exposing them to near UV or visible light.

Due to the sensitive nature of working with a virus such as coronavirus, it was crucial for Kell to be part of the team, since the work had to be done in cooperation with the UNM School of Medicine, which has BSL-3 lab facilities that are essential to doing study on the highly-contagious active virus, Ista said.

Whitten said he is hopeful that this discovery can quickly be put into use. He has a company called BioSafe Defenses that he said has hired a former Environmental Protection Agency official to help expedite the regulatory process in taking this discovery to market. He anticipates that once a material is approved, it will be only a matter of months before wipes, masks and other products are in the marketplace.

He said their research has found that adding the material into wipes would add only pennies per wipe. Additionally, the material could be added into masks and other personal protective equipment, changing the game for businesses such as gyms, airlines, cruise ships, groceries, health care facilities, schools and many more industries. In addition to coronavirus, these products could also help eliminate infections by the common cold, seasonal flu and other viral and bacterial infections that plague millions of people annually, causing loss of work and school time.

There is a limitless market for this, he said.

He added that the current pandemic is likely not the last such public health crisis we will see, so even after a vaccine for coronavirus is available, such products could be useful in combatting a wide variety of viruses and bacteria, including the flu or common cold.

Were not just thinking about COVID but other pathogens and any viral agents, Whitten said. We want to be ready for the next pandemic.

This research was funded by a grant from the National Institutes of Health.

Continued here:
Let there be light: UNM Newsroom - UNM Newsroom

Using CRISPR-Cas9 gene editing, she systematically disabled five shared leg-patterning genes in Parhyale and in insects, and found those genes corresponded to the six leg segments that are farthest from the body wall. Parhyale, though, has an additional, seventh leg segment next to its body wall. Where did that segment go, she wondered?

And so I started digging in the literature, and I found this really old idea that had been proposed in 1893, that insects had incorporated their proximal [closest to body] leg region into the body wall, she said.

But I still didnt have the wing part of the story, she said. So I kept reading and reading, and I came across this 1980s theory that not only did insects incorporate their proximal leg region into the body wall, but the little lobes on the leg later moved up onto the back and formed the wings. I thought, wow, my genomic and embryonic data supports these old theories.

It would have been impossible to resolve this longstanding riddle without the tools now available to probe the genomes of a myriad of organisms, including Parhyale, which the Patel lab has developed as the most genetically tractable research organism among the crustaceans.

In addition to his role as MBL director, Patel is appointed at UChicago asa professor of Organismal Biology and Anatomy,and ofMolecular Genetics and Cell Biology.

People get very excited by the idea that something like insect wings may have been a novel innovation of evolution, Patel said.But one of the stories that is emerging from genomic comparisons is that nothing is brand new; everything came from somewhere. And you can, in fact, figure out from where.

Citation: Knockout of crustacean leg patterning genes suggests that insect wings and body wall evolved from ancient leg segments,Bruce and Patel,Nature Ecology & Evolution, Dec. 1, 2020. DOI: 10.1038/s41559-020-01349-0

Funding: National Science Foundation

Adapted from anarticle originally posted by the Marine Biological Laboratory

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How insect wings evolved from the legs of an ancestral crustacean - UChicago News

SALT LAKE CITY Researchers at University of Utah Health's Huntsman Mental Health Institute have detected more than 20 genes that may play a role in suicide.

The research is the first of its kind, and a Utah mother who is still grieving doesn't find the results surprising.

Michelle Nelson stands in the bright kitchen of her 101-year-old house in Salt Lake City.

"Amethyst, opalite and crystal," she said, picking up the small stones from a dish on the counter.

She collects them to help her heal because picking up the pieces after loss is daunting.

"I take Roan everywhere I go," she said.

Nelson collects heart rocks stones that naturally form into a heart shape which she finds outside.

"It's like a gift from nature that reminds me of him," Nelson said.

Two years ago, her 16-year-old son, Roan McClain, died by suicide.

"It was the biggest shock of my life," she said. "You think your kids are always going to be okay."

Her family has a history of suicide.

In a new study, researchers at the Huntsman Mental Health Institute discovered 22 genes that could have a role in suicide deaths. It establishes that suicide is partially heritable independent of a shared environment.

"We looked at over 3,400 samples from individuals who had lost their lives to suicide in Utah," said Dr. Anna Docherty with the Huntsman Mental Health Institute.

The study, among the first comprehensive genome-wide analyses of suicide death, also found significant genetic cross-connections to psychiatric diseases and behaviors associated with suicide, researchers said.

"Understanding that there is a strong genetic component will destigmatize the subject of suicide," Docherty said.

The goal of the research is to inspire discussions among families and with their healthcare providers to know when to get support, Docherty said.

"If you have a family history of suicide, it really pays to learn about all of the myriad risk factors and ways that you can really promote health in your family."

For Nelson, it inspires hope.

"Maybe, if we could look at our kids and say, 'Hey, you really are at risk. What can we do to get ahead of this?'" she said.

Scientists hope identifying these genes could lead to better predicting who's at risk and finding better ways to help them.

In the meantime, Nelson continues to find comfort in nature, and her collection of heart rocks.

"When you lose someone close to you, your whole life changes," she said. "You have to notice the little things. You have to go back to those small things, like the rocks."

Next, researchers plan to dig into the molecular genetics of suicides to understand the links, and to find drug therapies.

If you or someone you love needs help, call the Utah Crisis Line at 801-587-3000.

If you or someone you know is struggling with thoughts of suicide, call the suicide prevention hotline at 1-800-273-TALK.

Crisis Hotlines

Online Resources

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University of Utah researchers discover genes linked to suicide - KSL.com

KARACHI: On the pattern of the Centre for Disease Control and Prevention (CDC), Atlanta, United States, Pakistan has been trying to establish its own CDC, for which preparations have been in an advanced stage, to deal with epidemics of communicable and non-communicable diseases along with emerging infectious ailments and pandemics like Covid-10, and advise the national and provincial governments in dealing with national health emergencies, The News has learnt.

Yes, we are in the advanced stage of establishing a Centre for Disease Control Pakistan like they have in the United States, China and many other countries of the world. Establishing such an institute was my long-standing dream, which is going to materialise within a few weeks or months, Special Assistant to Prime Minister (SAPM) on Health Dr Faisal Sultan told The News on Thursday.

He said a draft legislation had been prepared for the establishment of the proposed institute and it was being vetted by experts while his team was also in the process of looking for epidemiologists, microbiologists, molecular genetics experts, virologists and other experts to be part of the centre.

Either this institute would be established through a [presidential] ordinance or an Act of Parliament but all the legal formalities are being completed in this regard. This dream of mine is going to materialise very soon but it would be a great service to the nation, Dr Sultan said, adding that not only him but several other infectious diseases and public health experts had been feeling the need for having such an institute in Pakistan for very long.

He maintained that after every crisis and emergency, a need was felt to establish centres like the National Command and Operation Centre (NCOC) was established after the Covid-19 pandemic and the National Emergency Operation Centre (NEOC) was set up for polio eradication. He added that this reactionary practice should come to end now and there should be a permanent institution like the CDC Atlanta to deal with such emergencies and plan for future threats.

To a query, Dr Sultan said the governments of the US, China and England had offered their assistance for establishing the CDC Pakistan, adding that in addition to foreign governments, Pakistani health experts working in the US, Europe and other parts of the world were also very enthusiastic in this regard and willing to help the country in having a world-class centre for disease control and prevention.

I have spoken to the ambassadors of the United States and China and the British High Commissioner in Pakistan and they all are willing to help us in this regard. There are several leading Pakistani health scientists and experts who are working at such institutions and they too are very enthusiastic and willing to support us in this endeavour, the SAPM maintained.

When asked when he felt the need for the establishment of a CDC like centre in the presence of the National Institute of Health (NIH), Islamabad, he said the NIH in its present form was not fulfilling the function of a centre for disease control and prevention despite having a national laboratory.

The NIH has a different function and it is now heading in a right direction under its current leadership but unfortunately it is not serving the purpose for which it was established. Our proposed centre for disease control would be a quite different institution, which would gather information about diseases, analyse them and recommend actions and give guidance to the authorities on all aspects of health, Dr Sultan said, adding that after its establishment, there would be no need for setups like the NCOC and the NEOC.

The CDC Pakistan would not only be working on the prevention and control of infectious and non-infectious diseases in Pakistan but it would also be keeping an eye over road traffic accidents, other disasters involving trauma and emergencies in the country and presenting its recommendations to lower these incidents as well as managing them properly, he remarked.

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Preparations in advanced stage for establishing disease control centre on pattern of CDC Atlanta - The News International

NewsClint Chan Tack3 Days Ago

UWI Professor of Molecular Genetics and Virology Christine Carrington has told the population that any covid19 vaccine administered in TT will be safe.

Her assurances were supported by statements from epidemiologist Dr Avery Hinds and nurse Grace Sookchand, manager of the Health Ministry's expanded programme on immunisation, about strategies for the vaccine's administration.

Modernas mRNA-1273, Oxford University and AstraZenecas AZD1222, and Pfizer and BioNTech's BNT162 are the three candidate vaccines which are currently undergoing phase three trials.

At the virtual health news conference on Monday, Carrington said there was an "avalanche of neatly packaged misinformation" about these vaccines.

She explained the reason extensive trials are done on vaccines is to ensure that they work.

"Long before reach phase three trials, you have other stages of trials where you are looking specifically at safety."

To date, Carrington continued, the vaccines appear to be very safe, She added that they would not have been administered to 30,000 people in the phase three trials if this was not so. But Carrington said additional safety information about the vaccines would be obtained in the phase three trials.

Hinds reiterated that the first phase of vaccination will focus on people who are most exposed to covid 19. This includes frontline responders (such as health care workers), people over 60 and people with illnesses such as cancer. He said as additional doses of the vaccine are received, policies and strategies will be elaborated to cover the wider population."

On the vaccination of prisoners, Hinds explained this was the responsibility of the Prison Service's medical personnel. He said the ministry, through the county medical officers of health, provides the service with guidance and technical support if needed.

Hinds also said PCR testing and antigen testing (which is soon to be rolled out) are the main strategies for covid19 testing in TT, and the latter will provide "an additional layer of testing capacity."

Antibody testing is not being used now, he said, because "we are testing to reduce the risk of spread in active cases, and antibodies only show up later on in your disease process."

Sookchand said chillers to store a covid19 vaccine will be placed at the Couva Medical and Multi-Training Facility, Nipdec's Central Stores in Chaguaramas and a location in Tobago.

She explained the specific type of chiller to be used will be influenced by the characteristics of the vaccine acquired. Sookchand added that ultra-low-temperature freezers would be sourced if necessary.

She also said health facilities for the administration of phase one of the vaccine have been identified and staff are being trained.

With TT having consistent vaccine administration levels in the high 90 per cent range, Sookchand was confident of a covid19 vaccine being successfully provided to the public.

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UWI professor: Covid19 vaccine will be safe - TT Newsday

To perform a Covid 19 test, the laboratory must be validated.In public laboratories the test has no cost, but it does generate an expense.Know the average cost of the Covid 19 test in private laboratories.

One of the main factors to avoid the spread of the coronavirus is the timely taking of a Covid 19 test to reduce the number of infections.According to the Ministry of Health, Mexico adds 105 thousand 655 deaths from Covid 19 and one million 107 thousand 71 accumulated confirmed cases.In the last few hours alone, 6,388 new confirmed cases of Covid 19 were registered in Mexico.Given this, the WHO assured that Mexico is in a bad situation in the face of the Covid 19 epidemic, which saw the number of cases and deaths double between mid and late November, warned Tedros Adhanom Ghebreyesus.

Related Notes:This is what a hospitalization for Covid 19 costs in MexicoCoronavirus: Medicines and healing materials cost 60% more in Mexico due to pandemicThe debts of Covid 19 patients and their families increase in Mexico

In addition to social isolation, another measure to contain the pandemic is to carry out the Covid 19 test in a timely manner and in Mexico there are 168 validated public and private laboratories.According to the Ministry of Health, the places authorized to test for Covid 19 have been growing, as it is necessary to have the recognition of the Institute for Epidemiological Diagnosis and Reference (InDRE).

There is the IMSS Division of Epidemiological Surveillance Laboratories that made three laboratories available in the entities.Support Laboratory for Epidemiological Surveillance of the Western Research Center (CIBO), Guadalajara, Jalisco.Laboratory of Support for Epidemiological Surveillance of the Center for Biomedical Research of the Northwest (CIBIN), Monterrey, Nuevo Len.Support Laboratory for Epidemiological Surveillance of the High Specialty Medical Unit in Yucatn (UIMY).The Laboratories to Support Epidemiological Surveillance (LAVES) are also available:National Institute of Respiratory Diseases.National Institute of Medical Sciences and Nutrition Salvador Zubirn.General Hospital of Mexico.November 20 Hospital (ISSSTE).37 Central Laboratory of Epidemiology, CMN La Raza (IMSS).Also in the public sector are:Childrens Hospital of Mexico, Federico Gmez.Hospital Central Sur Alta Especialidad PEMEX.New Civil Hospital of Guadalajara, Dr. Juan I. Menchaca .Molecular Biology and Biosafety Laboratory of the Naval Medical Center.Laboratory of Microbiology and Molecular Diagnosis of the Department of Immunobiochemistry, National Institute of Perinatology.Regional Hospital of High Specialty of Ixtapaluca.Virology Laboratory of the National Institute of Pediatrics.Infectology Laboratory of the National Rehabilitation Institute, Luis Guillermo Ibarra Ibarra.Central Military Hospital, dependent on the General Directorate of Military Health and the Secretariat of National Defense.Hospital Jurez de Mxico.

ABC Medical Center, Observatory Campus.Angeles Interlomas HospitalOlartey Akle, Bacteriologists.Lister Laboratories.Biomedical Laboratories of Mrida.LABIOMOLA.Spanish Hospital of Mexico City.South Medical.Aries Diagnostic Group.CARPERMOR Laboratory.ORTHIN Specialized Reference.Puebla Clinical Laboratories.Worthy Health.Jurez Laboratory.BIOQUIMIA Corporate Group, Siglo XXI.LSG Clnicos Mexicali.LANS, Reference Laboratories.Molecular Diagnostic Laboratory AL Gens.Diagnostic Molecular Biology (BIMODI).Molecular Genetic Pathology (PGM Laboratory).Central DNA.Clinical Diagnostic Advisors.Vitagenesis.Genodiagnostics.Laboratory of Surgical Pathology and Cytology of Puebla.GENOLIFE.Certus Laboratory.Specialized Developments in Biotechnology and Molecular Diagnosis, (Denatbio).Laboratory of Specialized Genetic Analysis Mexico, (LAGEM).Alfonso Ramos Laboratory.DIAGNOMOL Laboratories.Analytical and Diagnostic Unit,San jose hospital.LSD Clinical Analysis Diagnosis.La Hoz clinical diagnoses.Mrida Clinical Laboratories.SERVACARE.Immunological Specialties Laboratories.Christus Muguerza Laboratory.Hospital San ngel Inn University.Clinical Laboratory of the Campestre.Chontalpa Laboratories.Micro-Tec.Santa Maria Group.CENEBA,Diagnostic Image.LACLICSA Laboratories.CEDIMI Laboratories.Diagnostic and Associated Laboratories.PrimeLab Molecular Diagnostics.SIMNSA Molecular Biology Laboratory.GD Technologies.Huella Gnica, SA de CV

Also in some public universities they take the Covid 19 test sample.Center for Research in Health Sciences and Biomedicine (CICSaB), Autonomous University of San Luis Potos.Department of Genetics and Molecular Physiology of the Institute of Biotechnology (IBT) of the Autonomous University of Mexico (UNAM).Bioprocess Development and Research Unit of the National School of Biological Sciences (UDIBI-ENCB) of the National Polytechnic Institute (IPN).

Biosafety Laboratory for the Diagnosis and Research of Emerging Diseases, Cinvestav.Department of Cellular and Developmental Biology, of the Institute of Cellular Physiology, of the UNAM.Virology Laboratory, Institute of Biomedical Research, UNAM. Laboratory of Microbial Molecular Immunology of the Faculty of Medicine, UNAM.Infectious Diseases Research Laboratory, UNAM.Institute of Immunodeficiencies and HIV Research of the University Center for Health Sciences, University of Guadalajara (Ude-G).Laboratory for the Diagnosis of Emerging and Reemerging Diseases of the UdeG.CIR-Biomedical Virology Laboratory of the Autonomous University of Yucatn.Molecular Medicine Laboratory, of the Autonomous University of Zacatecas Francisco Garca Salinas.Molecular Microbiology Laboratory, of the Autonomous University of Quertaro.PABIOM Laboratory, of the Autonomous University of Chihuahua.Genomic Services Laboratory (Labsergen) of Cinvestavs Advanced Genomics Unit.Diagnostic and Research Laboratory of the Autonomous University of Guerrero.National Laboratory of Agricultural, Medical and Environmental Biotechnology of the Potosino Institute of Scientific and Technological Research.Food and Development Research Center, in Hermosillo, Sonora.Food and Development Research Center, in Mazatln, Sinaloa.Food and Development Research Center, in Culiacn, Sinaloa.National Institute of Genomic Medicine.National Laboratory of the Autonomous University of Nayarit.Biosafety Laboratory, Center for Nanosciences and Nanotechnology, UNAM.Molecular Diagnostic Laboratory of the University of Colima.Preclinical Research Unit of the UNAM.Biosafety Laboratory of the Ensenada Center for Scientific Research and Higher Education.Bioseguro Laboratory of the Center for Biological Research of the Northwest.Clinical Services Unit of the Autonomous University of Quertaro.Infectology Laboratory, Autonomous University of Nuevo Len.Molecular Biology Laboratory of the University Center of the Coast University of Guadalajara.Reference Laboratory Analysis and Diagnosis in Aquaculture Health, Hermosillo Unit.Center for Molecular Diagnosis and Personalized Medicine, University of Monterrey.Proteogenic Unit, Institute of Neurobiology, UNAM.Virology Laboratory of the Center for Research and Assistance in Technology and Design of the State of Jalisco.Research Unit Faculty of Veterinary Medicine and Zootechnics, UNAM.Laboratory of the Transdisciplinary Institute for Research and Services of the UdeG.Campus CUSUR Laboratory, of the UdeG.Molecular Virology Laboratory of the Cell Dynamics Research Center of the Autonomous University of the State of Morelos.Yucatan Scientific Research Center.Center for Genomic Biotechnology, National Polytechnic Institute, Reynosa, Tamaulipas.

The Covid 19 tests have no cost in public hospitals and state laboratories, although they generate an expense of approximately 1,492 pesos, according to the Director of Diagnosis and Reference of the InDRE, Irma Lpez Martnez, while in the private laboratories of the City of Mexico offer the test for a price between 3,300 and 3,400 pesos.Irma Lpez Martnez explained that it is necessary to first evaluate the type of test, because although they are all polymerase chain reaction (PCR), they have different methodologies. Remember that only a doctor can evaluate if you need to take a Covid 19 test according to the symptoms you present.

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Tech : Public and private laboratories validated to perform the Covid 19 test - Explica

STINGing viruses without interferon

The adaptor protein STING induces the production of antiviral interferons in response to the cyclic dinucleotide 23-cGAMP generated as a danger signal during viral infection of mammalian cells. Drosophila have a STING ortholog but do not produce interferons. Cai et al. found that exogenously administered 23-cGAMP protected Drosophila against multiple DNA and RNA viruses in a manner dependent on STING and the transcription factor Relish, an ortholog of NF-B. This antiviral immunity did not involve autophagy, a cellular process in which STING plays an evolutionarily conserved role and that can restrict viral replication, or RNA interference, an antiviral response in Drosophila. These results suggest that 23-cGAMP as a viral danger signal is evolutionarily older than previously suspected and that STING was incorporated into the interferon response during vertebrate evolution.

We previously reported that an ortholog of STING regulates infection by picorna-like viruses in Drosophila. In mammals, STING is activated by the cyclic dinucleotide 23-cGAMP produced by cGAS, which acts as a receptor for cytosolic DNA. Here, we showed that injection of flies with 23-cGAMP induced the expression of dSTING-regulated genes. Coinjection of 23-cGAMP with a panel of RNA or DNA viruses resulted in substantially reduced viral replication. This 23-cGAMPmediated protection was still observed in flies with mutations in Atg7 and AGO2, genes that encode key components of the autophagy and small interfering RNA pathways, respectively. By contrast, this protection was abrogated in flies with mutations in the gene encoding the NF-B transcription factor Relish. Transcriptomic analysis of 23-cGAMPinjected flies revealed a complex response pattern in which genes were rapidly induced, induced after a delay, or induced in a sustained manner. Our results reveal that dSTING regulates an NF-Bdependent antiviral program that predates the emergence of interferons in vertebrates.

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23-cGAMP triggers a STING- and NF-Bdependent broad antiviral response in Drosophila - Science

Harvard Medical School scientists have successfully restored vision in mice by turning back the clock on aged eye cells in the retina to recapture youthful gene function.

The teams work, described today (December 2, 2020) in Nature, represents the first demonstration that it may be possible to safely reprogram complex tissues, such as the nerve cells of the eye, to an earlier age.

In addition to resetting the cells aging clock, the researchers successfully reversed vision loss in animals with a condition mimicking human glaucoma, a leading cause of blindness around the world.

The achievement represents the first successful attempt to reverse glaucoma-induced vision loss, rather than merely stem its progression, the team said. If replicated through further studies, the approach could pave the way for therapies to promote tissue repair across various organs and reverse aging and age-related diseases in humans.

Our study demonstrates that its possible to safely reverse the age of complex tissues such as the retina and restore its youthful biological function, said senior author David Sinclair, professor of genetics in the Blavatnik Institute at Harvard Medical School, co-director of the Paul F. Glenn Center for Biology of Aging Research at HMS and an expert on aging.

Sinclair and colleagues caution that the findings remain to be replicated in further studies, including in different animal models, before any human experiments. Nonetheless, they add, the results offer a proof of concept and a pathway to designing treatments for a range of age-related human diseases.

If affirmed through further studies, these findings could be transformative for the care of age-related vision diseases like glaucoma and to the fields of biology and medical therapeutics for disease at large, Sinclair said.

For their work, the team used an adeno-associated virus (AAV) as a vehicle to deliver into the retinas of mice three youth-restoring genesOct4, Sox2 and Klf4that are normally switched on during embryonic development. The three genes, together with a fourth one, which was not used in this work, are collectively known as Yamanaka factors.

The treatment had multiple beneficial effects on the eye. First, it promoted nerve regeneration following optic-nerve injury in mice with damaged optic nerves. Second, it reversed vision loss in animals with a condition mimicking human glaucoma. And third, it reversed vision loss in aging animals without glaucoma.

The teams approach is based on a new theory about why we age. Most cells in the body contain the same DNA molecules but have widely diverse functions. To achieve this degree of specialization, these cells must read only genes specific to their type. This regulatory function is the purview of the epigenome, a system of turning genes on and off in specific patterns without altering the basic underlying DNA sequence of the gene.

This theory postulates that changes to the epigenome over time cause cells to read the wrong genes and malfunctiongiving rise to diseases of aging. One of the most important changes to the epigenome is DNA methylation, a process by which methyl groups are tacked onto DNA. Patterns of DNA methylation are laid down during embryonic development to produce the various cell types. Over time, youthful patterns of DNA methylation are lost, and genes inside cells that should be switched on get turned off and vice versa, resulting in impaired cellular function. Some of these DNA methylation changes are predictable and have been used to determine the biologic age of a cell or tissue.

Yet, whether DNA methylation drives age-related changes inside cells has remained unclear. In the current study, the researchers hypothesized that if DNA methylation does, indeed, control aging, then erasing some of its footprints might reverse the age of cells inside living organisms and restore them to their earlier, more youthful state.

Past work had achieved this feat in cells grown in laboratory dishes but fell short of demonstrating the effect in living organisms.

The new findings demonstrate that the approach could be used in animals as well.

Lead study author, Yuancheng Lu, research fellow in genetics at HMS and a former doctoral student in Sinclairs lab, developed a gene therapy that could safely reverse the age of cells in a living animal.

Lus work builds on the Nobel Prize winning discovery of Shinya Yamanaka, who identified the four transcription factors, Oct4, Sox2, Klf4, c-Myc, that could erase epigenetics markers on cells and return these cells to their primitive embryonic state from which they can develop into any other type of cell.

Subsequent studies, however, showed two important setbacks. First, when used in adult mice, the four Yamanaka factors could also induce tumor growth, rendering the approach unsafe. Second, the factors could reset the cellular state to the most primitive cell state, thus completely erasing a cells identity.

Lu and colleagues circumvented these hurdles by slightly modifying the approach. They dropped the gene c-Myc and delivered only the remaining three Yamanaka genes, Oct4, Sox2 and Klf4. The modified approach successfully reversed cellular aging without fueling tumor growth or losing their identity.

In the current study, the researchers targeted cells in the central nervous system because it is the first part of body affected by aging. After birth, the ability of the central nervous system to regenerate declines rapidly.

To test whether the regenerative capacity of young animals could be imparted to adult mice, the researchers delivered the modified three-gene combination via an AAV into retinal ganglion cells of adult mice with optic nerve injury.

For the work, Lu and Sinclair partnered with Zhigang He, HMS professor of neurology and of ophthalmology at Boston Childrens Hospital, who studies optic nerve and spinal cord neuro-regeneration.

The treatment resulted in a two-fold increase in the number of surviving retinal ganglion cells after the injury and a five-fold increase in nerve regrowth.

At the beginning of this project, many of our colleagues said our approach would fail or would be too dangerous to ever be used, said Lu. Our results suggest this method is safe and could potentially revolutionize the treatment of the eye and many other organs affected by aging.

Following the encouraging findings in mice with optic nerve injuries, the team partnered with colleagues at Schepens Eye Research Institute of Massachusetts Eye and Ear Bruce Ksander, HMS associate professor of ophthalmology, and Meredith Gregory-Ksander, HMS assistant professor of ophthalmology. They planned two sets of experiments: one to test whether the three-gene cocktail could restore vision loss due to glaucoma and another to see whether the approach could reverse vision loss stemming from normal aging.

In a mouse model of glaucoma, the treatment led to increased nerve cell electrical activity and a notable increase in visual acuity, as measured by the animals ability to see moving vertical lines on a screen. Remarkably, it did so after the glaucoma-induced vision loss had already occurred.

Regaining visual function after the injury occurred has rarely been demonstrated by scientists, Ksander said. This new approach, which successfully reverses multiple causes of vision loss in mice without the need for a retinal transplant, represents a new treatment modality in regenerative medicine.

The treatment worked similarly well in elderly, 12-month-old mice with diminishing vision due to normal aging. Following treatment of the elderly mice, the gene expression patterns and electrical signals of the optic nerve cells were similar to young mice, and vision was restored. When the researchers analyzed molecular changes in treated cells, they found reversed patterns of DNA methylationan observation suggesting that DNA methylation is not a mere marker or a bystander in the aging process, but rather an active agent driving it.

What this tells us is the clock doesnt just represent timeit is time, said Sinclair. If you wind the hands of the clock back, time also goes backward.

The researchers said that if their findings are confirmed in further animal work, they could initiate clinical trials within two years to test the efficacy of the approach in people with glaucoma. Thus far, the findings are encouraging, researchers said. In the current study, a one-year, whole-body treatment of mice with the three-gene approach showed no negative side effects.

Reference: 2 December 2020, Nature.DOI: 10.1038/s41586-020-2975-4

Other authors on the paper include Benedikt Brommer, Xiao Tian, Anitha Krishnan, Margarita Meer, Chen Wang, Daniel Vera, Qiurui Zeng, Doudou Yu, Michael Bonkowski, Jae-Hyun Yang, Songlin Zhou, Emma Hoffmann, Margarete Karg, Michael Schultz, Alice Kane, Noah Davidsohn, Ekaterina Korobkina, Karolina Chwalek, Luis Rajman, George Church, Konrad Hochedlinger, Vadim Gladyshev, Steve Horvath and Morgan Levine.

This work was supported in part by a Harvard Medical School Epigenetics Seed Grant and Development Grant, The Glenn Foundation for Medical Research, Edward Schulak, the National Institutes of Health (grants R01AG019719, R37AG028730, R01EY026939, R01EY021526, R01AG067782, R01GM065204, R01AG065403, R01EY025794, R24EY028767 and R21EY030276), and the St. Vincent de Paul Foundation.

Relevant disclosures: David Sinclair is a consultant to, inventor of patents licensed to, board member and equity owner of Iduna Therapeutics, a Life Biosciences company developing epigenetic reprogramming therapies, and an unpaid consultant to Zymo Research, an epigenetic tools company. Yuancheng Lu, Luis Rajman and Steve Horvath are equity owners of Iduna Therapeutics. George Church and Noah Davidsohn are co-founders of Rejuvenate Bio.

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Scientists Reverse the Aging Clock: Restore Age-Related Vision Loss Through Epigenetic Reprogramming - SciTechDaily

Princess Margaret scientists have revealed how stem cells are able to generate new blood cells throughout our life by looking at vast, uncharted regions of our genetic material that hold important clues to subtle biological changes in these cells.

The finding, obtained from studying normal blood, can be used to enhance methods for stem cell transplantation, and may also shed light into processes that occur in cancer cells that allow them to survive chemotherapy and relapse into cancer growth many years after treatment.

Using state-of-the art sequencing technology to perform genome-wide profiling of the epigenetic landscape of human stem cells, the research revealed important information about how genes are regulated through the three-dimensional folding of chromatin.

Chromatin is composed of DNA and proteins, the latter which package DNA into compact structures, and is found in the nucleus of cells. Changes in chromatin structure are linked to DNA replication, repair and gene expression (turning genes on or off).

The research by Princess Margaret Cancer Centre Senior Scientists Drs. Mathieu Lupien and John Dick is published in Cell Stem Cell, Wednesday, November 25, 2020.

"We don't have a comprehensive view of what makes a stem cell function in a specific way or what makes it tick," says Dr. Dick, who is also a Professor in the Department of Molecular Genetics, University of Toronto.

"Stem cells are normally dormant but they need to occasionally become activated to keep the blood system going. Understanding this transition into activation is key to be able to harness the power of stem cells for therapy, but also to understand how malignant cells change this balance.

"Stem cells are powerful, potent and rare. But it's a knife's edge as to whether they get activated to replenish new blood cells on demand, or go rogue to divide rapidly and develop mutations, or lie dormant quietly, in a pristine state."

Understanding what turns that knife's edge into these various stem cell states has perplexed scientists for decades. Now, with this research, we have a better understanding of what defines a stem cell and makes it function in a particular way.

"We are exploring uncharted territory," says Dr. Mathieu Lupien, who is also an Associate Professor in the Department of Medical Biophysics, University of Toronto. "We had to look into the origami of the genome of cells to understand why some can self-renew throughout our life while others lose that ability. We had to look beyond what genetics alone can tell us."

In this research, scientists focused on the often overlooked noncoding regions of the genome: vast stretches of DNA that are free of genes (i.e. that do not code for proteins), but nonetheless harbour important regulatory elements that determine if genes are turned on or off.

Hidden amongst this noncoding DNA - which comprise about 98% of the genome - are crucial elements that not only control the activity of thousands of genes, but also play a role in many diseases.

The researchers examined two distinct human hematopoietic stem cells or immature cells that go through several steps in order to develop into different types of blood cells, such as white or red blood cells, or platelets.

They looked at long-term hematopoietic stem cells (HSCs) and short-term HSCs found in the bone marrow of humans. The researchers wanted to map out the cellular machinery involved in the "dormancy" state of long-term cells, with their continuous self-renewing ability, as compared to the more primed, activated and "ready-to-go" short-term cells which can transition quickly into various blood cells.

The researchers found differences in the three-dimensional chromatin structures between the two stem cell types, which is significant since the ways in which chromatin is arranged or folded and looped impacts how genes and other parts of our genome are expressed and regulated.

Using state-of-the-art 3D mapping techniques, the scientists were able to analyze and link the long-term stem cell types with the activity of the chromatin folding protein CTCF and its ability to regulate the expression of 300 genes to control long-term, self-renewal.

"Until now, we have not had a comprehensive view of what makes a stem cell function in a particular way," says Dr. Dick, adding that the 300 genes represent what scientists now think is the "essence" of a long-term stem cell.

He adds that long-term dormant cells are a "protection" against malignancy, because they can survive for long periods and evade treatment, potentially causing relapse many years later.

However, a short-term stem cell that is poised to become active, dividing and reproducing more quickly than a long-term one, can gather up many more mutations, and sometimes these can progress to blood cancers, he adds.

"This research gives us insight into aspects of how cancer starts and how some cancer cells can retain stem-cell like properties that allow them to survive long-term," says Dr. Dick.

He adds that a deeper understanding of stem cells can also help with stem cells transplants for the treatment of blood cancers in the future, by potentially stimulating and growing these cells ex vivo (out of the body) for improved transplantation.

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Mapping out the mystery of blood stem cells - Science Codex