Category Archives: Epigenetics

Epigenetics, or the study of biological changes that occur due to different chemical marks that alter the expression of our genes, proves that the beneficial effects of yoga penetrate deep into our minds and bodies and may even touch the very code of life that makes us who we are.

Do you feel stressed too often? Dont worry, youre not alone. The growing number of mentalhealth cases in India are pointing in the direction of a pressing need for attention. Research hasfound the top few sources of increasing stress in the lives of over one billion Indians to be money,work, family responsibilities, and health concerns.

Too much stress can take a significant toll on ones health. Not being able to copewith stress can lead to chronic diseases and accelerated ageing (but dont think about that toomuch, or risk adding it to your already lengthy list of issues inducing stress). If you have been trying to takemeasures to reduce therapy and have not achieved the desired outcome, there is still hope.

Epigenetic research has found that the ancient art of meditation, particularly mindfulmeditation, has numerous health and stress-reducing benefits.Yoga is the most ancient form of basic human wellness or unity of mind-body or in biologicalterms state of homoeostasis Homeo (resembling) stasis (equilibrium). In this state, all chemicalsand biochemicals in the body are in absolute balance state. All hormones calibrated (no excess orlittle testosterone, estrogen, cortisol), no excess or little adrenaline, dompamine(feel good) purged of all environmental toxins. Yoga helps in rhythmicbreathing which allows mind-body calibration resulting inneuroplasticity that fine tunes the brain or CNS to get calmer.

(The author isfounder,Vantage Enterprise)

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Get to the core with epigenetics - Deccan Herald

Through early adulthood, exposure to new experienceslike learning to drive a car or memorizing information for an examtriggers change in the human brain, re-wiring neural pathways to imprint memories and modify behavior. Similar to humans, the behavior of Florida carpenter ants is not set in stonetheir roles, whether it is protecting the colony or foraging for food, are determined by signals from the physical and social environment early in their life. But questions remain about how long they are vulnerable to epigenetic changes and what pathways govern social behavior in ants.

Now, a team led by researchers in thePerelman School of Medicine discovered that a protein called CoREST, a neural repressor that is also found in humans, plays a central role in determining the social behavior of ants. The results, published inMolecular Cell, also revealed that worker ants called Majors, known as brawny soldiers that protect colonies, can be reprogrammed to perform the foraging rolegenerally reserved for their sisters, the Minor antsup to five days after they emerge as an adult ant. However, the reprogramming is ineffective at the 10-day mark, revealing how narrow the window of epigenetic plasticity is in ants.

How behavior becomes established in humans is deeply fascinatingwe know its quite plastic especially during childhood and early adolescencehowever, of course, we cannot study or manipulate this experimentally, saysthe studys senior authorShelley Berger, the Daniel S. Och University Professor in the departments of Cell and Developmental Biology and Biology, and director of the Penn Epigenetics Institute. Ants, with their complex societies and behavior, and similar plasticity, provide a wonderful laboratory model to understand the underlying mechanisms and pathways."

Read more at Penn Medicine News.

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Reprogramming ant 'soldiers' - Penn: Office of University Communications

The Epigenetics Market report includes the research on production, consumption, revenue, CAGR, market share and growth rate, and forecast (2013-2023) of the major players.

Global Epigenetics Market Report helps the readers to maximize their profits and business making ventures by gaining complete insights of Epigenetics Industry. The latest developments and growth opportunities in Epigenetics market are covered. Development trends, revenue analysis, Global Epigenetics market share and market dynamics are presented to optimize the business. The vital Epigenetics insights, opportunities in existing and emerging segments are explained. An in-depth analysis of the present state of Epigenetics, progressive future trends, and comprehensive analysis based on Epigenetics type, application, players and regions are covered. The report thoroughly analyzes the Epigenetics competitors, SWOT analysis, industry chain structure and production process view.

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The top Epigenetics industry players are:

Major Players in Epigenetics market are:

RocheMerck & Co. Ltd.QiagenCellcentric LimitedValirx PlcThermo Fisher ScientificSigma-Aldrich CorporationEisai Co. Ltd.Oncoloys Biopharma Inc.AbcamDiagenodeSyndex PharmaceuticalsActive Motif Inc.Chroma TherapeuticsZymo Research CorporationIllumina IncNovartis AG

The report begins with an introduction, definition, objectives, and Global Epigenetics market scope. The industry size is estimated based on market value, revenue, concentration ratio and Epigenetics growth rate. The report covers major industry trends, drivers, threats which will depict the market growth during the forecast period. The complete perspective in terms of Epigenetics revenue, geographical regions namely North America, Europe, Asia-Pacific, Middle-East & Africa, and South America is portrayed. The key information on distributors and suppliers of Epigenetics industry represents the present and forecast trends.

A complete market tactics are explained in this research report which is segmented into by product type, end users, applications, etc. Forecast industrial statistics will roll on the way to predict the futuristic industry growth opportunities. The pertinent facts and market numbers are presented which are gathered from regulatory authorities. Dominating factors influencing the growth of dominant market players and their position is analyzed in this report.

Global Epigenetics Industry news, plans & policies, market drivers, analysis of upstream raw material suppliers and downstream buyers of Epigenetics is carried out in this report. On regional and country level market share, production value, gross margin analysis, consumption ratio, import-export scenario, and SWOT analysis is covered. Global Epigenetics business forecast study enlists the market price (in USD) and volume forecast for every region, product kind, and applications.

The business approach and growth statistics implemented by Global Epigenetics industry competitors will lead to a competitive edge in the industry. The production and demand statistics of Epigenetics driven by evolving market segments across different regions, type and application are mentioned in this report. The value chain analysis and market share for varied Epigenetics players are covered. The consumption statistics for the mentioned type, applications and regions are enclosed in the report. This report will help you in analyzing the industry scenario and characteristics of Global Epigenetics market.

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Detailed analysis of segment and subsegment are given below

Types of Global Epigenetics Industry:

DNA MethylationHistone MethylationHistone AcetylationLarge Noncoding RNAMicroRNA ModificationChromatin Structures

Applications of Global Epigenetics Industry:

OncologyNon-OncologySolid TumorsLiquid TumorsInflammatory DiseasesMetabolic DiseasesInfectious DiseasesCardiovascular Diseases

The Epigenetics market competitive factors leading to heavy market demand and development scope is analyzed thoroughly. Also, a special focus on distributors, manufacturers, traders, and suppliers is provided. The market share, units produced and consumption in every consecutive year is obtained from this research report. All the latest qualitative and quantitative information along with sales data are presented. Also, the detailed analysis of past performance of Global Epigenetics Industry and business-related moves with the present scenario is studied.

Report Summary:

In the first section, the Epigenetics Market report presents industry overview, definition, and scope. The second part briefs about the Epigenetics industry bifurcation by Type, Application and Geographical regions. The major market players of Epigenetics Industry and their market share, revenue analysis, sales margin, etc. are presented in this in depth analysis. The Export-Import policy, resources utilized, raw materials study, demand and supply of the products is offered for the better understanding of new entrants and their market position is explained. The Strength, Weakness, Opportunity & Threats are analyzed in such a manner that it will be helpful for future decision making processes. The Porters Five Force analysis is examined along with the 5-year forecast scope of the report for Epigenetics industry. All these will lead to successful & profitable business plans and informed moves. Additionally, the sources of research, research processes, findings, conclusions are offered.

Why Select This Report:

Complete analysis on market dynamics, market status, and competitive Epigenetics view is offered.

Forecast Epigenetics Industry trends will present the market drivers, constraints and growth opportunities.

This research report will help to understand how the market will grow in the coming years lets say next 5-6 years and so on.

All vital Epigenetics Industry verticals are presented in this study like Product Type, Applications and Geographical Regions.

This in-depth market study will help to analyze the and take informed decision in their respective field.

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Global Epigenetics Market CAGR, Share and Growth Rate, and Forecast (2013-2023) of the Industry Major Players. - Montana Ledger

Is 50 the new 30? Or is 30 the new 50?

A New York Citybased biotech company, Elysium Health,believes it can help you figure that out with unprecedented levels of accuracy using a simple, though spendy ($500)at-home saliva test called Index. You spit in a vial, send the sample back to Elysium, wait four to sixweeks for processing, andvoil!receive a report indicating whether your biological age is younger, older, or the same as your chronological age.

Chronological age is, of course, all those trips youve made around the sun. Biological age, on the other hand, is how well youve held up during those tripsa measure of your physiological health. Scientists have been trying to determine biological age for at least 50 years, using various biomarkers (like cholesterol, blood glucose, skin elasticity, and vascular function, to name a few) and mathematical modeling. Only recently have researchers started using our DNA to evaluate age.

ElysiumsIndex calculates your biological age by looking at DNA methylation (DNAm), which is one of the ways genes are turned on or off. Methylation occurs when methyl groupsclusters of hydrogen atoms surrounding a carbon atomattach to the DNA and prevent their expression. Some patterns of methylation are inherited and occur naturally with age, but others are triggered by environment and lifestyle factors, like smoking, stress, exercise, and exposure to chemicals. DNAm isnt the only way genes may be modified, but it is the most common and has become an important player in the broader field of epigenetics, the science of gene expression. Epigenetic researchershave found that DNAm profiles correspond remarkably well with age-related biomarkers. So a researcher looking at a blind DNAm profile sample could conclude that it represents someone who is 50 years oldalthough the actual subject might be 40or 60.

Index came from asking two questions, says Elysium CEO Eric Marcotulli. First, can you measure aging itself?And second, what is the most accurate way to do that?

The answer to that first question appears to be yes, and the science behind it gained a lot of ground in 2011, with the creation of the epigenetic clock. That clockwas actually a formula for calculating age based on cellular health using DNAmdata, which was then correlated with large data sets like the National Health and Nutrition Examination Survey, the largest study ever conducted on population health. By comparing new DNAm samples with established patterns drawn from large studies,scientistscould estimate biological age, give or take a few years.

To answer the second questionhow to measure biological age with enough accuracy to be relevant for individualsMarcotulli tapped Morgan Levine, an assistant professor of pathology at Yale and a rising star in the field of aging research, to lead the Index project for Elysium. As a postdoc at UCLA, Levine worked with Steven Horvath, a human-genetics and biostatistics professor largely credited with creating the first epigenetic clock. With Horvaths help, Levine developed a more advanced version of the epigenetic clock. Where early versions gathered data from a few hundred DNAm sites on the genome, Levines was able to read data from 100,000 sites (Elysium is heralding this as revolutionary), allowing them to more reliably and consistently pinpoint biological age, along with your cumulative rate of agingthat is, how fast you are getting old.

Levine says she has put Index to the test herself, but her initial results werent as good as shed hoped, eventhough shes a lifelong runner with a pretty healthy lifestyle.Shebelieved she could score betterand decided to add high-intensity and strength training to her workout regimen. When she retested six months later, her biological age had improved. Strength and high-intensity training is one thing I thought might make a difference, she says. Thats not a scientific study, because its nof one, but in my own life, I want to figure out how to take control of aging and stay physically functioning for as long as possible.

Currently, Index only offers basic information on biological agea kind of overall health score. But future editions, says Levine, will be able to highlight different biological systems, where you may want to apply more effort toward improvement, like certain types of exercise or diet. Traditional health caremay only flag a health issue once it becomes a problem, like the onset of disease. Levine says Index may help people get a jump on health issues before they occur.

Its hard not to approacha new biotech product making grandiose claims with a large beaker of skepticism. The field is swamped with hucksters and marketing hype, forever stigmatized by megascandals like that of Theranos, the infamous biotech company that falsely claimed it could conduct advanced blood tests with tiny samples. Elysium insists its bringing new standards of scientific rigor and legitimacy to the marketplace, but theres reason for pause.

To date, Elysium has released just one other product: Basis, a supplement that increasesNAD+, a molecule essential for cellular health that diminishes with age. Basis was developed by MIT heavyweight Leonard Guarente, an Elysium cofounder. Since its release in early 2015, Basis (which costs$50 a month) has received mixed reviews from consumers, who have reported everything from renewed energy to side effects like sleeplessness and body aches. Elysium has conducted several double-blind, placebo-controlled clinical trialsthe gold standardand shown that the supplements raise NAD+ as much as 40 percent. But molecular science is exceedingly complex, and the notion that a single supplement will provide miraculous anti-aging benefits is itself a large pill to swallow. Its worth noting that neither Basis (a supplement, not a pharmaceutical) nor Indexrequired FDA approval.

Still, consumers are increasingly interested in taking more control of their health, and biotech companies are eager to provide tools that, they claim, will help them do so. The problem is that the line between science and marketing gets squishy fast. Index not only complements Basis, it drives sales of the supplement:Doubt our claims? Take our test to see if its working!

And if it does work, then what? Like a lot of biotech for consumers, a central question is what to do with the information. Index results will come with some lifestyle recommendations, though its unclear what those will look likeexactly. Will they be any different than general advice weve already heard? Move a lot, hydrate, eat whole foods, get some decent sleep, go outside, spend time with loved ones. You know the drill.

Whether consumers will embrace their own epigenetic clock in a box is anyones guess. The novelty alone may give it at least an initial splash; you can almost imagine a new crop of younger-than-their-chronological-age bio influencers popping up on social media (save us now). But who knows. The science is certainly compelling, and Index could prove to be an insightful way to test lifestyle tweaks, dietary experimentation, and other interventions that might improve health. And if it does really make 50 look more like 30, five hundredbucks may seem like a bargain.

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For $500, This Company Will Tell You How Well You're Aging - Outside

Theres no shortage of data highlighting how humans have impacted their environment. From climate change to Feng Shui, people constantly alter their surroundings to suit their needs. What is less understood is how environment can impact human development.

In Vitro Fertilization (IVF) gives many hopeful parents the opportunity to create a family. With the use of donor eggs, hopeful parents-to-be often assumed that the child wouldnt share any of their characteristics. However, with the development of epigenetics, this isnt altogether true.

Epigenetics is the study of how lifestyle choices can impact your DNA, while not actually changing it. External factors can include environment, what we consume, how we are raised and even how we feel about our world. If we think about a DVD, we cant alter the content, but we can adjust the picture, language preferences, volume settings, etc. Through the lens of IVF with donor eggs, epigenetics observes how non-genetic characteristics (or markers) can be transmitted from parent to offspring.

Stress, exercise, proper nutrition during pregnancy, the general health status of both partners, these are all factors that can affect how your babys genes are expressed, Carrie Nicols, organic farmer and student of holistic nutrition tells Parentology. Even if you use donor eggs, your biography can inform your childs biology.

What does expression mean? Nicols likens the process to light switches. Certain characteristics can be turned on or off depending on the stimuli, she says. Once we know what triggers them proper nutrition for example we can figure out how to manipulate them for better overall health.

If epigenetics has the potential to alter or affect health conditions such as obesity, diabetes and even psychiatric illness, it stands to reason physical and hormonal changes that occur during pregnancy would certainly be impacted. In 2009, researchers at the University of Pittsburgh Medical Center suggested our social environment, including maternal care, can induce epigenetic changes.

Nicols agrees. While factors such as nutrition, stress and hormones wont change your genetic code directly, they can certainly leave an imprint to pass along to your children.

The impact of environment on an embryo in utero cant be overstated. Researchers studied the effects of malnutrition on women and the children they produced between 1944 and 1945. Not surprisingly, mothers with limited access to food produced underweight babies.

What was surprising was that those babies grew up to have underweight babies, even after the effects of food insecurity were felt. Of those babies that survived, malnutrition had changed a marker in their genetic code, leading researchers to determine that the nine months in utero were the most important period in determining how much or how little genetic activity genes will produce during a persons life.

If a woman is undergoing IVF using donor eggs, this argument proves particularly relevant. Dr. Norbert Gleicher, Medical Director and Chief Scientist at the Center for Human Reproduction (CHR) in New York, agrees. While (women) do not contribute maternal genes to the baby, they determine, in very significant ways, how these genes will work during the individuals lifetime, he tells Parentology.

Moreover, Gleicher says a womans impact on her embryo while its in utero not only affects her unborn child. Maybe even more importantly, (genes that are) programmed during the in utero period can also be inherited into future generations. Therefore, you may be important not only for how your own childs genes function, but also how your grandchilds genes will be functioning, even if you used donor eggs.

Ultimately, pregnancy demands a change in your lifestyle. Regardless of whether you have IVF using donor eggs or conceive naturally, the incentive to eat well, rest and take care of yourself is paramount to the health and well-being of your child.

Your IVF JourneyCenter for Human ReproductionBio News UK

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Nurture vs Nature: Epigenetics, IVF and the Donor Egg - Parentology

The nature-vs.-nurture contributions to human behavior have fueled a long-running debate while serving as a continued topic of research. In the latest chapter, Kathleen Krols study of 101 babies and their mothers, the University of Virginia scientist sheds light on the role played by early parental care in the development of the oxytocin system.

Oxytocin is a hormone in the human nervous system that plays a key role in a persons ease in forming relationships, caregiving and other social behavior.

While epigenetic modifications chemical changes that have the capacity to affect how genes are expressed, without altering the underlying genetic sequence occur naturally in the body and are involved in a number of vital processes, they also can be influenced by the environment, as was suggested in Krols study.The findings by Krol, a Hartwell Postdoctoral Fellow in UVAs Department of Psychology, reveal that babies who are in close proximity to an attentive caregiver and who are talked to earlier by their caregiver display a reduction of epigenetic modification on the oxytocin receptor gene, ultimately suggesting an increase in receptors for oxytocin in the first 18 months of their lives.

We wanted to explore the hypothesis that maternal behavior early on might critically impact the development of the oxytocin system in infants, said Krol, who began this work as a Ph.D. student with Tobias Grossmann at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany. Krol has since been working in Jessica J. Connellys lab in UVAs Department of Psychology, where she trained in the molecular biology techniques required for this multidisciplinary research.

Our findings provide the first evidence that the endogenous oxytocin system, known for its essential role in processes crucial for human social interaction, is malleable in infants and can be shaped by the early caregiving environment, Krol said.

Krols findings were published recently in a Science Advances research article with co-senior authors Connelly and Grossmann, associate professors in the Department of Psychology, as well as with Robert G. Moulder, a graduate student in quantitative psychology. Krol spearheaded this multi-lab collaboration as part of her Hartwell Postdoctoral Fellowship, in which she proposed to analyze this data in Connellys lab.

Krol continues her research in Connellys lab, which seeks to understand the relationship between DNA methylation (a process by which methyl groups are added to specific sites on the gene) of the oxytocin receptor and individual differences in behavior in humans. She also continues to collaborate with the UVA Baby Lab, directed by Grossmann, which researches the brain processes underpinning social interaction and cognition during infancy.

Katies work is the first to connect maternal-infant interaction with epigeneticchangein the human oxytocin system, Connelly said.This foundational work allows us to begin experiments to describe the precise mechanisms through which this change occurs, determine how long change can happen, and, of course, the downstream effects of this change from infants to adults.

After recruiting 101 mothers with 5-month-old babies, Krols team began their study by observing how each mother interacted with her baby during a five-minute play period, when the two were left alone with toys and a book. These sessions were scored by researchers based on how physically close the mother was to her baby, how much eye contact they shared and other factors. Researchers collected DNA from saliva samples taken from mother and child at the five-month visit as well as a visit more than a year later, when infants were 18 months old.

During these interactions, we coded things like, How close was the mother to her infant? How talkative was the mother? How much did she vocalize with the infant? How much did the infant smile and vocalize back? Krol said.

Researchers also asked the mothers to fill out questionnaires requesting details on infants negative temperament, such as how their infants responded at home to intense sounds and lights, different odors, textures and other stimuli.

Krol then relied on DNA samples to look at a gene that codes for the receptor for oxytocin, measuring modifications to the oxytocin receptor gene. Higher levels of DNA methylation have been associated with the down tuning of genes, Krol said. While the mothers levels of methylation did not fluctuate between the two visits, the babies DNA samples told a different story.

The babies who had experienced more involved play with their mothers during the observed sessions showed a decrease in methylation, while those who had received less attention displayed an increase. This could indicate that babies who are offered more opportunities for involved play develop more oxytocin receptors. At the same time, Krol said, those same babies the ones with decreased levels of methylation that may be tied to more active play appeared to display reduced negative temperament as reported by parents.

Heightened DNA methylation at 18 months was associated with increased negative affect and sensitivity to intense lights, sounds and textures, Krol said. Our findings suggest that maternal engagement may have the potential to help regulate the oxytocin system in their offspring, which in turn can influence their overt behavior.

It is likely too soon to draw specific conclusions on parenting advice based on this research, which focuses on one specific genetic difference. However, Krol said their findings could offer guidance for caregivers of infants and young toddlers.

Successful interactions with caregivers are crucial as infants begin to navigate the social world. These foundational interactions may ultimately facilitate their lifetime capacity to affiliate and engage with others, Krol said. We demonstrate one potential mechanism by which early experience epigenetically establishes and shapes trajectories of human development.

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Study: Maternal Interaction May Influence the Epigenetics of Baby's Social Development - University of Virginia

Photo: David Giesbrecht/SHOWTIME

Over the course of its five-year run, Showtimes The Affair spanned the better part of a half-century, from a kismet connection between frustrated writer and father of four Noah Solloway (Dominic West) and depressive Montauk waitress Alison Bailey (Ruth Wilson), to their trysts impact on multiple families across generations. Its been an epic and erratic path to tonights series finale, fomenting with drama onscreen and off, but the 90-minute capper was in a word profound. Over the course of The Affairs final few episodes, showrunner Sarah Treem and her team justified the rigor of moving on from the departure of multiple cast principals by reimagining the series as a time-jumping genre hybrid, ultimately sticking a deeply touching, humane landing. It may well be the best sendoff of its kind since Six Feet Under, even if The Affairs sum total was nearly as flawed as its leads.

Two days prior to her babys swan song, we caught up with Treem to talk about the high-wire act of ending a high-concept project; Noahs remarkable redemption; the characters final, dreamlike detour through seafood purgatory; and the soundtrack choice that justified the journey.

How do you cope with the lag between wrapping a long-running show on your end and the eventual public verdict?To be totally honest, we were down to the wire with post-production. [Laughs.] Theres a lot of feelings involved. Weve been doing VFX stuff to the bitter end, so I cant quite anticipate what its going to feel like when its over, but I guess Im going to find out this Sunday. In some ways Im probably dragging it out just because Im terrified.

In terms of the VFX, some shows have aged main characters more successfully than others. Were you conscious of where your effort might fall on that spectrum?I honestly dont watch enough television to be aware. I was definitely worried that we werent going to make them look good, but they did a really good job with Noah, and Dominic West also did a really good job with the old version of Noah, and it was a challenge he was excited to embrace. His old-man characterization felt like a really different character to me.

It does come across that West and Maura Tierney are really caring and committed about their characters to the end. Has it felt that way to you, and how crucial is that when you did lose some principal cast going into this season?I love those actors, as actors and as people. And I agree that they cared so deeply about these characters, and we took them on such an intense ride. Dominic said something like, Sarah challenged me in every way I could think of. And I was like, Well, I could think of other ways. [Laughs.] I think the two of them together getting so much space to play at the very end was nice for them and nice for us. We were behind the camera just basically enjoying it. Dominic gave me this card at the end that had his future face on it, but he was peeling the face off, so there was this horrifying image, and it was hilarious. But he said playing the character of Noah made him a better actor and a better man, which was a nice thing to say after all these years.

The fact that the finale zeroes in on Noahs redemption might surprise people, given how Helen had emerged as arguably the central character and the fact that Noah had been through a Me Too reckoning. Are you anticipating how people might read into all that?I know. [Laughs.] Im getting ready for all of it. I would say that, at the end of the day, this was a story about this marriage and the choices and relationships between these two people. Theres that classic aphorism: Nobody knows what happens in anybody elses marriage. And I think thats basically true. The choices we make for our lives in terms of who were going to spend them with, those are not group decisions and we dont make them for the right political purposes, or even for our children. We make them for ourselves, and sometimes they dont make a lot of sense to other people. In terms of what led these two characters back together, all I can say is it just felt like the right thing to do.

Another big theme this season was inherited trauma. Was the actual science behind that something you came across midstream during the series and assimilated into the story, or was it always in your back pocket?Thats such an interesting question. I dont remember. There was always a sense that this was going to be a story about how this one act impacted not just Noah and Alison, but their extended families and then children in the future. I did start to think about inherited trauma early on in the process. The idea of epigenetics definitely came in later. I dont quite remember when we started talking about that, but somebody introduced me to the work of Rachel Yehuda, and it did seem to be a science that explained what we understood anecdotally and emotionally in terms of how trauma gets passed on in families. I understood that from a storytellers perspective, but I didnt know there was a science behind it, so that was very exciting.

The character of EJ was the vessel for much of the epigenetics dialogue, but he also turns out to be Vic and Sierras son. Some might have connected the dots, since baby EJs name is Eddie, but had you hoped it would be a revelation in the finale?Yes, I did. We struggled with that, in terms of how much we were going to reveal about that character to understand he was this other character grown up. Eddie being his name was the first component. At one point he said, My father died before I was born, and we considered taking that line out but left it in. And then he really likes old movies, which we thought was a funny thing only we were gonna pick up on, because his grandmother was a film star. But some people actually picked up on that too, so I was pretty impressed with the audience. I personally have a problem when stories do a reveal that audiences could have never seen coming, even if they were paying close attention. I think thats a bit of a cheat, so I wanted to put in some bread crumbs about Eddie. I dont know if we ended up putting in too many, but I think its fine either way. Hes part of the story, so if you saw it beforehand, its okay.

In terms of other speculative aspects, Joanie jokes to Noah that the Lobster Roll is like seafood purgatory. Just to be clear, are the flash-forward scenes intended to be the concrete reality of those characters, or is it open to interpretation?I think you can interpret it any way you want. [Laughs.] But I did love the seafood-purgatory line, because from Joanies perspective, its like, Where the hell is she? Its not an active restaurant, there isnt anybody out here.

Its like Joe Versus the Volcano in Montauk.[Laughs.] Totally. Thats exactly right. Whether you interpret it as realism or not, the thing is so much happened where shes sitting in this place that she has never seen, so in some ways, it all does seem like a bit of a dream or a story. Once the past becomes the past, it becomes less real.

Is it fair to say that when Joanie describes her job as trying to save the world from drowning, its an apt metaphor for reconciling the enormity of her familys trauma?Yes, exactly. Its devastating when you think about it that way, because of the futility of it. But yes, its the only way shes been able to survive.

And how should audiences reconcile that Ben is neither cuffed nor killed by episodes end?My feeling was that this is not a show that brings people to justice. Its not a show where people pay for their crimes in the way you want them to. Noah pays for other peoples crimes, but he never pays for his, or he pays for them over a long period of time. And Helen never pays for the crime that she committed, and Alison doesnt deserve to die, and Cole commits his own crimes and is never brought to justice for them. Thats not what this show is about. This show is about the long-term effects of the choices we make and how nobodys gonna save you from yourself. Joanie thinks she wants Ben brought to justice, and thinks thats what she needs, and then she doesnt get it. But in not getting it, it sends her on this spiral back to Noah. What she really needs is not for her mothers killer to be brought to justice, but to forgive her mother and therefore to forgive herself, so she gets what she needs in the end.

Ben going to prison or dying by her hand is not going to break the cycle of trauma. Whats going to break the cycle of trauma is change, and doing what her mother couldnt do, which is going home and staying with the people who love her. Shes a child of so much abandonment, and then she breaks the cycle at the very end. In a show that is so much about looking at narrative and the way people construct it and lie to themselves and others when theyre telling their own stories, I didnt want to do a very simple, bad-guy-gets-caught-and-punished at the end. That feels like a betrayal of the meta-story were telling. I wanted to it to be a story about how Joanie ends up changing her narrative about herself.

So you never felt constrained by structuring the show around different points of view?No, I like it. Its funny, Im writing this new series right now, and two of the biggest characters are Hedy Lamarr and Louis B. Mayer, and were breaking their storylines separately in one episode, and I keep forgetting that we can go outside their POV. [Laughs.] Im like, Well, I dont know how were gonna tell that part about the plane. And someones like, Well, were just gonna show it. Its like, Oh, fuck. To be honest, I really like this sort of [POV] storytelling. It provides a nice challenge and true character-based exploration of a story Im personally comfortable and happy in. Im actually having an issue breaking out of that.

At the end of the day, if the whole series was a roundabout way of encouraging audiences to listen to the Waterboys, was it worth it?

[Laughs.] I think it was, yeah.

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The Affair Showrunner Sarah Treem Explains Why That Ending Felt Like The Right Thing to Do - Vulture

In late February 2019, the National Science Foundation, or NSF, gathered a group of scientists from widely different disciplines who rarely communicate let alone collaborate into one room, provided skilled facilitators to push their ideas to the edge of innovation, then stepped back to see what would happen.

Ideas Labs like these undergird the NSFs $36 million dollar investment in its Understanding the Rules of Life portfolio. Its aim is to accelerate development in two key areas of science and engineering research: building a synthetic cell and epigenetics.

Cheryl Kerfeld, MSU Hannah Distinguished Professor in the MSU-DOE Plant Research Laboratory and Department of Biochemistry and Molecular Biology attended this particular Ideas Lab outside of Washington, D.C. She explained that what happened was akin to the wheel people getting together with the suitcase people a breakthrough.

Kerfeld will lead this unlikely team of scientists that includes five research groups from universities across the nation in a $3.4 million Rules of Life grant to engineer a synthetic cell.

Kerfelds Rules of Life team members are: Christine Keating, professor of chemistry from Penn State University; Millie Sullivan, professor of chemical and biomolecular engineering from the University of Delaware; Vincent Noireaux, professor of physics from the University of Minnesota; Giovanna Ghirlanda, professor of chemistry from Arizona State University; and Barbara Harthorn, professor of anthropology from the University of California Santa Barbara.

We are going to take building blocks from different scientific disciplines that would never naturally get together physics, biology and materials chemistry to build a functional, multi-compartmental and fat-free cell, or ProteoCell, Kerfeld said. Outside of the Ideas Lab context, we never would have self-assembled into a team, and it never would have occurred to me to build a cell without lipids.

Although the first and fundamental goal of the project is to make a synthetic cell without lipids, the project also has significant implications in the production of biomaterials and biofuels in the United States.

There are important and introspective questions that need to be asked as we develop new technologies, Kerfeld said. A cell without lipids is highly artificial, and if we are successful, it may lead to a self-propagating system that could be harnessed for industrial applications.

There are ethics around this as well as the fundamental questions that we are asking, like what is life?

With NSFs encouragement and support, the team will also study the societal perceptions of a synthetic cell as well as how engineering a new kind of cell might also change the scientists.

The NSFs Rules of Life is one of the grand challenges of biology, Kerfeld noted, and MSU should be proud that we are leading an elite group of high caliber researchers and faculty able to address these questions.

For more information about NSFs Rules of Life Initiative, please visit: https://www.nsf.gov/news/special_reports/big_ideas/life.jsp.

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Unlikely gathering of scientists generates extraordinary research team to create the fat free cell - MSUToday

Tissues from biopsies are routinely preserved by formaldehyde fixation and embedding in paraffin wax. These samples provide a vast archive of disease and comparative healthy tissue information. Unlocking the chromatin within this archive would provide the field of epigenetics with a continuing supply of tissue from a multitude of disease states, allowing examination of the in vivo histone modifications and transcription factor occupation of gene promoters from large cohorts. Many of these samples have been preserved for up to 20 years giving the added advantage of the knowledge of patient outcomes of the disease. Extraction of chromatin from FFPE tissue is difficult, time consuming and fraught with problems. The fixation process can result in the damage of many of the protein epitopes, leaving a lower proportion of epitopes available to be recognised by the specific antibodies in ChIP.Chromatrap FFPE ChIP provides a superior extraction system which results in a much higher yield of chromatin than comparable extraction methods providing more available protein for the ChIP antibody and an efficient immunoprecipitation.

This short technical note demonstrates the success of the Chromatrap FFPE ChIP kit in the extraction and analysis of chromatin from both human and animal tissue preserved using FFPE. Using chromatin immunoprecipitation (ChIP) targets are selectively and reproducibly enriched using the Chromatrap spin columns following extraction with Chromatrap FFPE ChIP kit reagents.

Formalin fixed paraffin embedded (FFPE) tissue is an invaluable source of DNA, RNA and chromatin from clinical and historical samples. Over a billion tissue samples, comprised mainly of FFPE tissue, are estimated to be stored in hospitals, tissue banks and laboratories worldwide [1]. The vast majority of pathology samples are stored as FFPE blocks for analysis such as immunohistochemistry (IHC). Researchers have already begun unlocking the potential of this tissue using DNA and RNA extraction for genomic and epigenetic analysis. In line with the requirements of the current era in personalised medicine, analysing larger sample cohorts to study numerous biomarkers used for targeted therapies and prognosis, detailed profiling of genomes is becoming increasingly important. Translating the potential of epigenetic profiles for new biomarker discovery and validation requires access to cohorts with associated patient information, diagnosis and treatment outcome. Archived tissue provides an advantage over fresh or frozen tissue in that it remains viable for further analysis over a longer time period, disease outcomes and additional clinical data are often collected long after biopsies are taken. Genotyping technologies have been successfully employed on nucleic acids from FFPE tissue to examine mutations in genes [2, 3] and gene expression [4]. Utilising the chromatin from these samples has proved more difficult due to extensive cross-linking and damage to protein epitopes resulting from the fixation process and the destruction of these proteins during typical DNA extraction protocols. Traditional DNA extraction protocols are designed to remove proteins [5] and often involve phenol extraction where the protein is separated in the interphase [6].Sample quality and availability remain limitations for high throughput genetic profiling [6]. As a result of the fixation process and the extensive cross-linking which occurs in the preparation of FFPE tissues DNA yield is often low, chemically modified and highly degraded [7]. Formalin fixation leads not only to cross-links between proteins and DNA but also between the strands of DNA themselves [8] which causes inhibition of downstream processes such as PCR [9]. Fixation conditions such as extremely low pH cause additional fragmentation of DNA which compounds poor PCR efficiency. In addition to the issues with the DNA component of the genetic material extracting chromatin from FFPE tissue brings its own set of unique challenges.The Chromatrap FFPE ChIP kit overcomes these difficulties using an optimised buffer system for extraction which results in a much higher yield of chromatin, leading to more protein epitopes available to ChIP antibodies. Coupled with the increased sensitivity, eliminating the need for high chromatin loading in the Chromatrap system this makes Chromatrap FFPE ChIP kit the perfect solution for epigenetic research utilising FFPE tissue.

FFPE sample preparationFFPE samples used in this study were rat uterine tissue (fixed for 18 hours in 10% formalin and soaked in 70% ethanol before embedding in paraffin wax, Figure 1a) and human breast tissue (Amsbio, Oxford UK), fixed in 10% neutral formalin for 24 hours before embedding in immunohistochemical grade paraffin wax (Figure 1b).Each tissue type was sectioned into 5 m slices using a microtome (Leica) and the slices placed into a microcentrifuge tube. 20 x 5 m slices of each tissue type were pooled into a microcentrifuge tube per extraction.Figure 1: Rat uterine and human breast tumour FFPE tissue Blocks.

Chromatin was extracted from the FFPE tissue blocks according to the Chromatrap FFPE ChIP kit protocol. Briefly, paraffin wax was removed from each sample by adding 1 ml Paraffin Removal Solution (PRS) to each tube and incubating samples on a rotating platform for 5 min at room temperature (RT). Tubes were subsequently centrifuged for 5 min at maximum speed at RT and the supernatant carefully aspirated. Fresh PRS was added to each sample and the preceding process repeated to a total of 3 washes in PRS. Following aspiration of the final PRS wash tissue was rehydrated by addition of 1 ml 100% ethanol and tubes were again incubated on a rotating platform for 5 min at RT. Samples were then centrifuged for 5 min at full speed at 4C before carefully aspirating the supernatant. The washing process was repeated with 70% ethanol, 20% ethanol and finally sterile distilled water. Following aspiration of the final distilled water, the pellet was resuspended in 1 ml FFPE Lysis Buffer and incubated for 30 min at RT on a rotating platform.Samples were centrifuged for 5 min at maximum speed at 4C, the supernatant was aspirated and the pellet resuspended in 500 l Digestion Buffer. Samples were homogenised by sonicating for 3 cycles of 30s on 30s off at 42% amplitude before addition of 1 l Shearing Cocktail. Samples were mixed by pipetting and incubated at 37C for 5 min before addition of Enzymatic Stop Solution. Pellets were collected by centrifugation, the supernatant carefully aspirated and samples resuspended in 500 l FFPE Extraction Buffer. Chromatin was extracted by 40 rounds of sonication 30s on 30s off at 42% amplitude. Soluble (supernatant containing chromatin) and insoluble (pellet of tissue debris) fractions were separated by centrifugation. To check the fragmentation and quality of the extracted chromatin 25l aliquots of each fraction were reverse cross-linked and proteinase K digested, measured using a Qubit fluorometer (Invitrogen) and analysed by agarose gel electrophoresis. From Figure 2 it can be seen that the chromatin is well sheared (fragments are between 100-500 bp) and of good concentration.

Figure 2: Agarose gel electrophoresis and Qubit measurements of chromatin extracted from rat and human FFPE tissue using the Chromatrap FFPE ChIP kit.

For the immunoprecipitation slurries were prepared according to the Chromatrap FFPE ChIP kit protocol. In each 1ml slurry 20 l of chromatin stock was used with either 4 g of anti-Histone H3 (Chromatrap Product Code: 700000) for the positive immunoprecipitation or non-specific mouse IgG for the negative immunoprecipitation. Inputs were prepared in parallel containing 20 l of the relevant chromatin stock, these were used for subsequent analysis and not subjected to ChIP enrichment. Immunoprecipitation was carried out as per the standard Chromatrap FFPE ChIP protocol. Briefly, slurries were incubated for 1 hour on an end to end rotator at 4C prior to loading onto to the relevant Chromatrap ProA ChIP column, followed by a series of quick and simple centrifugation washes. Chromatin was eluted following a 15 min incubation of the FFPE Elution Buffer on the column. Samples and Inputs were reverse cross-linked for 2 hrs before Proteinase K digestion for 1hr. Finally, samples were cleaned using the supplied Chromatrap FFPE purification columns and buffers and eluted in 50 l DNA Elution Buffer.

qPCR was carried out using primers which recognise either the human or rat GAPDH locus [10]. These primer sets generate amplicons <100bp for efficient analysis of highly fragmented FFPE DNA. Subsequent analysis enabled detection of precipitation and therefore, specific enrichment at these gene loci when compared with non-specific IgG. The percentage of real signal was calculated as a factor of the amount of input chromatin to enable relative analysis between samples. Error bars represent the standard error of the mean of triplicate ChIPs.

To demonstrate the application of the Chromatrap FFPE ChIP kit in the high yield extraction and excellent enrichment of chromatin from FFPE tissue the common epigenetic mark H3 was specifically enriched from chromatin extracted from FFPE rat uterine tissue and human breast tumour tissue.Excellent signal to noise is demonstrated following enrichment of the GAPDH locus in human (Figure 3) and animal chromatin (Figure 4) from FFPE tissue, using an antibody directed against H3. The sensitivity of the assay is illustrated by high positive antibody signal from very low chromatin concentrations and the superior selectivity by the low non-specific binding. The versatility of the assay allows excellent signal to be obtained from both 100 ng of human breast tumour chromatin or 1 g rat uterine chromatin.

The Chromatrap FFPE ChIP kit is the perfect assay kit for efficient extraction and immunoprecipitation of chromatin from complex formalin fixed paraffin embedded tissue from human and animal sources. The extraction protocol provides a high yield of chromatin from very difficult sample sources and the superior sensitivity of the unique solid state ChIP columns allows high real signal to be generated from low concentration chromatin. Coupled with shorter protocols and high throughput capability, these advantages make the Chromatrap FFPE ChIP kit a quick, versatile sensitive and reproducible assay for analysis of patient or research FFPE archives.

1. Tang, W., David, F. B., Wilson, M. M., Barwick, B. G., Leyland-Jones, B. R., Bouzyk, M. M. (2009). DNA Extraction from Formalin-Fixed, Paraffin-Embedded Tissue. Cold Spring Harb Protoc, pdb prot5138 (2009).2. Beadling, C., Heinrich, M. C., Warrick, A., Forbes, E. M., Nelson, D., Justusson, E., Levine, J., Neff, T. L., Patterson, J., Presnell, A., McKinley, A., Winter, L. J., Dewey, C., Harlow, A., Barney, O., Druker, B. J., Schuff, K. G., Corless, C. L. (2011). J. Mol diagn 13:504-13.3. Su, Z., Dias-Santagata, D., Duke, M., Hutchinson, K., Lin, Y. L., Borger, D. R., Chung, C. H., Massion, P. P., Vnencak-Jones, C. L., Lafrate, A. J., Pao, W. (2011). A platform for rapid detection of multiple oncogenic mutations with relevance to targeted therapy in non-small cell lung cancer. J. Mol diagn 13:74-84.4. Fanelli, M., Amatori, S., Barozzi, I., Minucci, S. (2011). Chromatin immunoprecipitation andhigh-throughput sequencing from paraffin-embedded pathology tissue. Nat Protoc. 6(12):1905-19.5. Fan, H., Gulley, M. L. (2001). DNA Extraction from Paraffin-Embedded Tissues. Molecular Pathology Protocols 49, 1-4.6. Pikor, L. A., Enfield, K. S., Cameron, H., Lam, W. L. (2011). DNA extraction from paraffin embedded material for genetic and epigenetic analyses. J Vis Exp. (49). pii: 2763.7. Bourgon, R., Lu, S., Yan, Y., Lackner, M. R., Wang, W., Weigman, V., Wang, D., Guan, Y., Ryner, L., Koeppen, H., Patel, R., Hampton, G. M., Amler, L. C., Wang, T. (2014). High-throughput detection of clinically relevant mutations in archived tumour samples by multiplexed PCR and next-generation sequencing. Clinical cancer research 20(8):2080-91.8. Lin, J., Kennedy, S. H., Svarovsky, T., Rogers, J., Kemnitz, J. W., Xu, A., Zondervan, K. T. (2009).High-quality genomic DNA extraction from formalin-fixed and paraffin-embedded samples deparaffinized using mineral oil. Anal Biochem. 395(2):265-79. Gilbert, M. T., Haselkorn, T., Bunce, M., Sanchez, J. J., Lucas, S. B., Jewell, L. D., Van Marck, E., Worobey, M. (2007). The isolation of nucleic acids from fixed, paraffin-embedded tissues-which methods are useful when? PLoS One. 2(6):e537.10. Barber, R. D., Harmer, D. W., Coleman, R. A., Clark, B. J. (2005). GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiological genomics 21,389-95.

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Unlocking the archive - Chromatrap ChIP from Formula Fixed Paraffin Embedded (FFPE) Tissue - Labmate Online

The concept of epigenetics is one that is easily misunderstood and even misused. This is obvious from premature claims that we epigenetically inherit the trauma of our ancestors or that epigenetics explains so-called past-life experiences. With epigenetics being increasingly evoked online and in the pages of the latest bestsellers, its important to explore what is actually known about the topic. While New Age entrepreneurs such as Deepak Chopra speak with confidence about being able to harness the powers of the epigenome for the benefits of human health, we need to keep in mind that far more is unknown about epigenetics than is known. Lets have a look at what we do know.

Firstly, without the epigenome human bodies simply would not be. Each one of our somatic (body) cells has the same genes, yet not all of these genes are active all at once or in the same ways. If they were, each cell would be the same in both form and function. Instead, the bodys organs and organ systems are composed of highly specialized cells each cell type has unique functions, appearance, and metabolic activity. In the case of muscle cells, for example, undifferentiated cells in the human embryo receive a become muscle signal. These cells respond by epigenetically activating specific genes and turning others off, which sets them on a direct course to becoming muscle cells. Other cells receive different signals to become one of around 200 other human cell types (such as liver, skin, or fat cells).

The epigenome is basically an additional layer of genetic information that controls or mediates specific cellular behaviors and transcription activity. Some liken the epigenome to software while the genome is the hardware. The main types of epigenetic mechanisms or marks include DNA methylation and histone modification. Epigenetic marks are established very early in development and function by shielding sections of DNA from transcription machinery or exposing sections of DNA to transcription machinery. Shielded DNA is synonymous with the off position while exposed DNA is synonymous with the on position. Once the marks are established, each cell will pass its same epigenetic state to new cells, thus maintaining cellular identity and function.

Some parts of the epigenome appear to be susceptible to environmental or external influence, but not all sections of the epigenome are equally vulnerable. The epigenetic state of cells can be altered in response to environmental factors such as excessive stress, abuse, poor diet, pollution, and smoking sometimes with beneficial or protective outcomes and sometimes with detrimental or destructive consequences. Harmful epigenetic changes have been observed in cancer and in cardiovascular, autoimmune, metabolic, and neurodegenerative diseases. Though some studies suggest that certain epigenetic changes may be reversed by chance or with intervention, epigenetic alterations tend to be stable once they are established and are then passed on through cell division within the individuals body. This suggests that preventing harmful epigenetic changes is a better strategy than trying to reverse them once they occur.

An individuals epigenome is particularly sensitive during gestation (while in the womb) and right after birth. This may explain why a womans use of alcohol or drugs during pregnancy can do so much damage to the unborn child, in the form of such conditions as fetal alcohol spectrum disorders (FASD). It may also explain why the existence of obesity and other metabolic disorders in pregnant women can lead to a much greater chance of lifelong health problems (such as diabetes and heart disease) and premature death in their offspring. Intrauterine conditions permanently shape offsprings body function and structure, metabolism, and likelihood of developing certain diseases both in the short-term and in the long-term.

The vast majority of epigenetic changes only affect the individuals somatic or body cells, and are thus not transmitted to offspring. Lacal and Ventura refer to these epigenetic changes as direct epigenetics changes to the epigenome that occur over the lifespan of one person due to various experiences they have had, choices they have made, and environments in which they have found themselves. Good examples of direct epigenetics are seen in identical twins. Identical twins (aka monozygotic twins) have the same DNA, yet they rarely look exactly the same they may grow to be slightly different heights, have different body weights, develop wrinkles and gray hair at different times, and so on. And while one twin may develop a particular genetic illness or autoimmune disease, the other may remain disease-free. Identical twins rarely have the same health profiles, and usually develop illness, age-related disease, and mortality at different times. In fact, identical twins tend to die more than 10 years apart. The majority of these differences are due to variations in the twins epigenomes, which are themselves due to varied experiences and environmental exposures that the twins had throughout the course of their lives. Many point to these types of examples to illustrate the substantial influence of environment, upbringing, and lifestyle on an individuals health and general wellbeing.

While most epigenetic information is erased and reprogrammed before it can be passed on to offspring, some epigenetic information may escape erasure and may thus be passed on to an individuals children (and potentially to subsequent generations). In mammals, there are at least two main periods of demethylation and remethylation once during the development of germ cells (the precursor cells that will become sperm and eggs), and once in the earliest stages of an embryos development. During demethylation, ancestral methylation patterns (key epigenetic marks) are almost completely erased. The regions that are not demethylated may represent hot spots of transgenerational epigenetic inheritance, according to a 2019 research review on epigenetic regulation by Wang et al. Its important to note that there has not yet been clear evidence in humans of transgenerational epigenetic inheritance, and that the topic of how transgenerational epigenetic inheritance might work in humans is highly debated.

Interestingly, the epigenetic erasure and reprogramming that occur in germ cells and in the early embryo can be interrupted, disturbed, or altered by certain external forces. These external forces include the use of assisted reproductive technology, such as in vitro fertilization (IVF), and the health, lifestyles, and diets of both of the parents. In this way, conditions like obesity in males can negatively impact germ cells before they become sperm (in the process of spermatogenesis), thus potentially leading to conditions such as diabetes in the next generation. While it was once thought that the health status of fathers upon conception was not important in terms of the future health of their offspring, and the focus was almost solely on the health of mothers instead, research in epigenetics has clearly indicated that the health status and lifestyle choices of both parents is crucial to the wellbeing of their future children.

Kristen Hovet is an American-Canadian journalist and writer who specializes in the areas of psychology, health, science, and the intersection of sociology and culture. Follow her on Facebook or Twitter at @kristenhovet

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'Easily misunderstood': 4 things to know about epigenetics, including the fact that most changes are not passed on to offspring - Genetic Literacy...