Sharpen your Mind with Meditation

Woman Meditating

It has long been known that meditation and other breath focused practices will increase the strength of focusing on tasks. A study by research staff at Trinity College Dublin and Global Brain Health Institute at Trinity have found the neurophysical connection between breathing and attention.

Yoga and other breath focused meditation practices have many cognitive benefits. Better focus, less wandering of the mind, an increase in positive emotions, arousal levels heightened and less emotional reactivity are among the benefits. Until the recent study there was no known direct neurophysical connection known between cognition and respiration or even suggested at.

For the first time breathing has been shown to directly affect levels of noradrenaline, a natural brain chemical messenger. Noradrenaline is released when a person is curious, challenged, exercised, focused and emotionally aroused. The brain gets help in growing new connections when noradrenaline is produced at the right levels. Breathing actually directly affects brain chemistry, our attention is enhanced and our brain health is improved.

The study found that participants who focus well during tasks that demand a great amount of attention had much greater synchronization between their attention and breathing. Those who focused poorly did not fair as well. The researchers believe that breath control practices might be used to stabilize attention and increase the health of the brain.

Yoga practitioners have known for over 2500 years that breathing influences the mind. The researchers looked at the connection that would explain the claims by breath measurements, reaction time and then activity of the brain in the locus coerulues, a small region of the brain stem where noradrenaline is produced. When a person is stressed, their brain produces too much noradrenaline and focusing is difficult. On the other hand, when we are feeling sluggish too little noradrenaline is produced. The researchers found that there is a ?sweet? spot of noradrenaline where our thinking, our memory and our emotions are much clearer.

The researchers found that when a person breathes in locus coeruleus activity is slightly increased and when a person breathes out it will decrease. This indicates that our attention is affected by our breathing, falling and rising with our cycle of breathing. By regulating and focusing on our breathing, we can optimize our level of attention. And by focusing on our attention level our breathing will become more synchronized.

Additional research could assist in developing non pharmacological therapies for those who might have attention compromised challenges such as traumatic brain injuries and ADHD, and additionally helping older people in cognition support. The research is particularly encouraging for further research in aging of the brain. As brains age they will typically lose mass, but less so in the brains of people who have practiced meditation for quite a while. Younger brains have less risk of dementia and meditation practices and techniques will strengthen the brain networks. A possible explanation for this is that by using breathing to control noradrenaline in the correct dose, we are helping our brain build new connections between the brain?s cells.

Buddhists and Yogis believe the breath to be a suitable object for meditation practices. Pranayama which is regulated breathing in a precise way and observing the breathing, causes changes in attention, arousal, and emotional control that are of great benefit to the person meditating.

Mindfulness (focus on breathing) and deep breathing practices (such as pranayama) are the traditional forms of breath focused practices. Mindfulness which emphasizes focus and attention will benefit those with compromised attention spans. The person focuses solely on the sensations of breathing but does not make any effort to control them. When a person?s level of arousal results in poor attention such as with driving while drowsy or a panic attack, this level of arousal could by controlled with controlled breathing.

To view the original scientific study click here: Coupling of respiration and attention via the locus coeruleus: Effects of meditation and pranayama

Stem Cell Therapy Effective at any Age

Stem Cells

Average life expectancy is continuing to rise, and with that trend age-related degenerative and chronic diseases increase also. New stem cell research which focuses on iPSCs or induced pluripotent stem cells, has shown promise for the aging population for cell based treatments such as organ replacement. The evidence shows that the age of donors does not appear to influence functionality. This offers promising hope for improvement in quality of life and longevity in older populations.

iPSCs are stem cells that can be generated directly from adult stem cells. They are derived by introducing products or specific sets of reprogramming factors into a given cell type. The review of current data on iPSCs has shown that older adults may benefit from iPSCs for personalized regenerative treatments and also for modeling genetic diseases. iPSCs may therefore be a viable alternative to embryonic stem cells (ESCs) which have limitations and include ethical concerns. It has been previously thought that ESCs are the only reliable source for cells that are young and do not accumulate the same level of damage to cells as do older cells.

Analysis does show that the donor age may interfere with how well the cells of their body will change into iPSCs. It does appear that regenerated stem cells may be rejuvenated resulting in some aging symptoms reversed. These iPSCs do show functionality improvement when analyzed with regular body cells. These cells can be discerned into mature body cells with younger stem cell donor efficiency. An elderly patient?s stem cells could be made into other cells and ultimately used for variety of treatments.

There are questions to be answered such as will cells from older donors indicate increased damaging mutations which is not typically seen in younger stem cell donors? And will mutations continue through the transformation?

iPSC research is still in its infancy and questions still remain. Stem cell function would need to be assessed for proper testing and stability of genes. Also protocols would need to be established so that various lab results can be compared. However, the research highlights the enormous potential for treating the elderly with iPSCs.

To view the original scientific study click here: Age Is Relative Impact of Donor Age on Induced Pluripotent Stem Cell-Derived Cell Functionality

Breakthrough in Genetic Editing

Gene Editing

Imagine being able to have your genes edited to eradicate errors and to greatly lengthen quality of life and life span. There are some people that are still active and independent at the age of 100 and live well beyond that. Generally those people also had long lived parents. What if the same genetic traits they inherited and more could be given to anyone?

Researchers at the Joint Institute of Metrology and Biology (JIMB) have recently developed MAGESTIC, a new CRISPR platform that is similar to a word processor which makes gene editing using barcodes. CRISPR which snips at DNA has been a clumsy tool making precision medicine or ?clipping? disease causing genetic mutations in patients virtually impossible. MAGESTIC or ?multiplexed accurate genome editing with short, trackable, integrated cellular barcodes? is being compared to a word processer that enables efficient search and replace functions for genetic material. This new platform was also able to produce an increase of sevenfold in survival of cells during the process of editing.

Previously, CRISPR required a very extensive understanding of how repair cuts with cells at a variety of sites across the genome could be controlled as needed. Because DNA strands are able to rejoin in very unpredictable ways, random mutations are likely to occur at the cut sites in the DNA of the cells. Additionally, many cells will not survive the process of editing at all. It has been extremely challenging building very accurate predictions of gene editing. Researchers want a more reliable way for programming CRISPR to be able to cut at targeted locations in the genome and then be able to direct cells for designed edits at the cut sites of the DNA. This can be accomplished by providing a donor DNA for the cell which the cell?s DNA repair machinery is able to use as a template for replacing the original sequence at the original cut site. However, the cell?s DNA repair system is complex and will not always behave predictably.

The cell searching for a DNA donor suitable for repairing a cut site is a huge challenge for the cell. The repair machinery of the DNA has to search through millions and even billions of DNA base pair sequences to be able to find the correct donor DNA. MAGESTIC has provided a significant advance in gene-editing technology by helping the cell search by artificially recruiting the DNA designed donor through a process called active donor recruitment which will recruit the donor DNA right to the cut site. This recruitment resulted in a sevenfold increase in the cell?s survival which was a change that resulted in increased effectiveness and efficiency.

The other feature that was different from CRISPR, was MAGESTIC?S new version of cellular barcode. Previously, researchers used small bits of circular DNA also known as plasmids to guide DNAs and to store barcodes for tracking designed mutations to each cell. The plasmids will multiply with cell growth and are inherited by both cells following cell division. With MAGESTIC the barcodes are integrated into chromosomes as opposed to single barcode per item correspondence which can vary widely in number resulting in 10 to 40 appearing in every cell.

Scientists do not know much about the function of the 0.l% of code that will vary between individuals in any population and is responsible for differences in susceptibility of disease. MAGESTIC helps to address the gap in understanding natural genetic variation through enabling individual genetic variant to be edited very precisely and compared to other genetic variants one by one. This results in help in uncovering which genetic differences will have cellular impact function. MAGESTIC will also edit all at one time in just a single test tube with every edit happening in any one of a million otherwise cells that are identical.

The researchers have reached a state where they have achieved sequencing the order of genome base pairs and are also able to change them. Additional research is needed to understand the edit sequencing.

To view the original scientific study click here: Multiplexed precision genome editing with trackable genomic barcodes in yeast

Fasting Boosts Gut Health

Fasting

A 24 hour fast can reverse age related decline of stem cell function in the gut according to a study conducted by biologists at the Massachusetts Institute of Technology. The study reveals that a metabolic switch occurs during a 24 hour fast. This switch results in a break down by cells of fatty acids rather than glucose. This change boosts gut stem cell regeneration in both old and young mice.

With age stem cells in the intestine start to lose their regeneration ability. This reduction makes it more difficult for people to recover from gastrointestinal conditions and infections since the stem cells in the intestine are the source for new cells. The biologists discovered they could boost stem cell regeneration using a molecule which activates the identical metabolic switch in the stem cells to induce burning fat rather than utilizing carbohydrates. This intervention could possibly be used for people who are recovering from a variety of conditions that effect the GI tract.

Fasting provides many positive effects in the intestines. It boosts regeneration of stem cells and can be useful in a variety of ailments which affect the intestines. Switching the intestinal stem cells to fatty acid oxidation significantly enhanced their function.

Omer H. Yilmaz, Assistant Professor of Biology at MIT, refers to stem cells in the intestinal wall as ?workhorses of the intestines?. And diet has a profound effect on the regeneration ability of tissue. It is known that a low calorie diet enhances longevity in humans. Intestinal stem cell function declines with aging which therefore interferes with the intestines ability to repair after damage. The researchers decided to focus on how a 24 hour fast might enhance the function of both old and young intestinal stem cells.

Once mice had fasted for 24 hours, the team removed stem cells from the intestine and transferred them to a culture dish. Their goal was to see if the cells would rise to
?mini intestines? which are known as organoids. Interestingly the team discovered that stem cells from the fasting mice resulted in double the regenerative capacity. Fasting had a profound effect on the intestinal crypts to make more organoids which are driven by stem cells. They observed this in both aged and young mice.

Additional studies which included sequencing RNA messenger of stem cells from the fasting mice showed fasting induced cells to change from the usual metabolism of carbohydrate burning to fatty acid metabolizing. The switch that occurs is through activation of transcription factors also referred to as PPARs. These turn on genes which are part of the metabolizing of fatty acids. The team discovered that by turning off this pathway, the fasting period would no longer boost regeneration. The team was also able to reproduce the positive effects of fasting to mimic the effects of PPARs by treating the mice with a molecule which mimics these effects. By activating just one metabolic pathway they were able to reverse some age phenotypes.

The next step is to study the process of the metabolic switch which provokes stem cells to strengthen their ability to regenerate. The team also plans to further research into how fasting might affect the ability of stem cells to regenerate other tissue types.

It may be possible to stimulate regeneration without having to fast for 24 hours which can be difficult for some people. Intermittent fasting involves eating during an 8 hour period each day and then fasting for 16 hours while drinking plenty of water. Some people do this every day. For those who have trouble going without food it can help a to eat a very low sugar diet including avoidance of high sugar fruits such as bananas, dates and dried fruit. All sweet foods and sweeteners tend to stimulate appetite and cause cravings.

To view the original scientific study click here: Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging

Zero Calorie Sweeteners Cause Weight Gain

Zero Calorie Sweeteners

In addition to common artificial sweeteners shown to change how the body processes fat and energy, a new study has revealed they can also cause health changes that are linked to obesity and diabetes. Because of the increased awareness of the health consequences associated with eating too much sugar, a dramatic increase in the consumption of zero calorie artificial sweeteners has occurred.

Artificial sweeteners are one of the most common food additives and are frequently consumed in diet and zero calorie beverages and other food products. The recent study is the largest examination to date which tracks biochemical changes in the body. Previous studies linked artificial sweeteners with negative health consequences; however the research had been mixed and raised questions about potential bias related to study sponsorship. The new study used an approach known as unbiased high throughout metabolomics after consumption of sugar and sugar substitutes. The tests were conducted in rats and cell cultures, and the researchers also looked at impacts on vascular health by studying how the substances affect the lining of blood vessels.

The research included feeding different groups of rats diets high in glucose or fructose, or aspartame or acesulfame (zero calorie artificial sweeteners). At the end of three weeks the researchers saw significant differences in the concentrations of fat, amino acids and biochemicals in blood samples. The results suggest that artificial sweeteners change how the body processes fat and gets its energy. They also found that acesulfame potassium appeared to accumulate in the blood with higher concentrations having a more harmful effect on the cells that line the blood vessels.

The researchers noted that in moderation the body can handle sugar. But when the system is overloaded over a long period the body machinery breaks down. They observed that replacing those sugars with the zero caloric artificial sweeteners led to negative changes in energy and fat metabolism.

The researchers note that the results do not provide a clear answer and further study is needed. But the question becomes, which is worse between sugar or artificial sweeteners? It is well known that high dietary consumption of sugar is related to negative health outcomes. The recent study suggests that the artificial sweeteners do too. If people chronically consume the foreign substances as with sugar also, the risk of health problems such as obesity and diabetes increases.

Experimental Biology 2018. “Why zero-calorie sweeteners can still lead to diabetes, obesity: Common artificial sweeteners shown to change how the body processes fat and energy.” ScienceDaily. ScienceDaily, 23 April 2018.

Raw Fruits and Vegetables are Good for Your Brain

raw-fruits-vegetablesA new study conducted by the University of Otago has revealed that fruits and vegetables consumed in their natural state promote better?brain health. The study which was published in Frontiers in Psychology found that for mental health in particular these food items in their ?unmodified? state retained more of their nutrients as opposed to consuming them cooked or canned.

A total of 400 young adults aged 18 to 25 from the United States and New Zealand participated in the study. This age group was chosen as they typically have the lowest vegetable and fruit consumption of all age groups and are additionally are at high risk for mental health disorders. The individual?s typical consumption of raw fruits and vegetables vs. cooked or canned were assessed. Their positive and negative mental health, lifestyle and demographic variables that could affect the association between vegetable and fruit intake were also taken into consideration such as health styles including sleep, exercise, unhealthy diet, chronic health conditions, ethnicity, gender and socioeconomic status.

Raw fruit and vegetable vs. canned or cooked fruits and vegetables predicted lower levels of mental illness symptomology such as depression, and improved levels of psychological wellbeing such as positive mood, life flourishing and satisfaction. The researchers found that these mental health benefits were significantly reduced for the canned and cooked fruits and vegetables indicating that consuming them in their natural state was more beneficial.

The top 10 raw foods related to better health were bananas, apples, carrots, dark leafy greens, grapefruit, citrus fruits, lettuce, fresh berries, kiwi fruit and cucumber. The research is increasingly beneficial as dietary changes may provide a safe, accessible and adjuvant approach to improving mental health.

An earlier study conducted by the University of Warwick?s Medical School which stressed the importance of consuming 5 or more fruits and vegetables per day, found that 33.5% of participants with high mental health wellbeing consumed at least that many servings per day. This compared to only 6.8% who ate less than one portion per day. This study did not focus on how the fruits and vegetables were consumed (fresh vs. cooked or canned), but additionally supports the findings of the importance of consuming 5 or more portions per day of these nutrient dense foods. This study found that along with smoking, fruit and vegetable consumption was the health-related behavior most consistently associated with high and low mental wellbeing. Both studies show that consuming fruits and vegetables may plan a potential role as a driver of not only better physical health, but also of mental wellbeing.

References:

Kate L. Brookie, Georgia I. Best, Tamlin S. Conner. Intake of Raw Fruits and Vegetables Is Associated With Better Mental Health Than Intake of Processed Fruits and Vegetables. Frontiers in Psychology, 2018; 9 DOI: 10.3389/fpsyg.2018.00487

S. Stranges, P. C. Samaraweera, F. Taggart, N.-B. Kandala, S. Stewart-Brown. Major health-related behaviours and mental well-being in the general population: the Health Survey for England. BMJ Open, 2014; 4 (9): e005878 DOI: 10.1136/bmjopen-2014-005878

New Stem Cell Niche Discovery

Adult Stem Cells

Researchers at Duke NUS Medical School headed by Gedas Greicius and Professor David Virshup, Director of the Programme in Cancer and Stem Cell Biology, have identified how the stem cell neighborhood, or niche, keep stem cells alive in the gut.

Stem cells have the ability to differentiate or develop into many different cell types in the body. They also serve as a repair system to replace damaged or aged cells. With the ability to regenerate, stem cells offer enormous potential to improve health, quality of life and lifespan.

Stem cells in our adult tissues live in very specific locations called stem cell niches where they provide an ideal and specialized neighborhood for stem cells. The stem cells in the niche are undifferentiated which means they have not changed into mature cells. This stem cell niche regulates how stem cells participate in tissue maintenance, regeneration and repair. The niche prevents stem cells from being depleted while also protecting the body from an over production of the stem cells. This understanding of stem cell niches is important in the field of stem cell therapeutics.

To understand the role of the niche, the researchers needed to identify the key cell types that regulate the numerous processes that take place within the cell niche. The key regulators in the intestinal cell niche are hormones called R-spondins and Wnts which are frequently expressed together. It has been unclear what type of niche cells make the R-spondins and Wnts.

The team studied the source and functional role of RSPO3, a R-spondin, and Wnts. RSPO3 is by far the most abundant R-spondin produced in the small intestine of a mouse. Using a mouse model, they identified the specific cell called a subepithelial myofibroblast as an essential source of both RSPO3 and Wnts. If these niche cells cannot make Wnts, mice will not develop adult intestines, and if they cannot make RSPO3 mice cannot repair the intestine after injury.

The work demonstrates the close interaction between epithelial stem cells and the niche that regulates them. The research provides new insights into the structure of the stem cell niche after injury and in health.

Reference: Gediminas Greicius, Zahra Kabiri, Kristmundur Sigmundsson, Chao Liang, Ralph Bunte, Manvendra K. Singh, David M. Virshup. PDGFRa pericryptal stromal cells are the critical source of Wnts and RSPO3 for murine intestinal stem cells in vivo. Proceedings of the National Academy of Sciences, 2018; 115 (14): E3173 DOI: 10.1073/pnas.1713510115

Is Canned Food Safe?

Intestinal Function

A new research study conducted by the students and faculty at Binghamton University, State University at New York, has revealed that food packaging could be negatively affecting the way in which our digestive tract operates. Zinc Oxide (ZnO) nanoparticles at doses that are relevant to what might be normally eaten in a meal or in a day, change the way our intestines absorb nutrients or your intestinal cell gene and protein expression.

ZnO nanoparticles are present in the lining of certain canned goods for their antimicrobial properties and to help prevent staining of sulfur-producing foods. In this study, canned tuna, corn, asparagus and chicken were studied using mass spectrometry to estimate how many particles might be transferred to the food. The findings revealed the food contained 100 times the daily dietary allowance of zinc. The researchers then looked at the effect the particles had on the digestive tract.

The researchers looked at how an animal model (chickens) respond to nanoparticle ingestion. The cell culture results are similar to results found in animals and that the gut microbial populations are affected. The effects of nanoparticles on intestinal cells have been looked at before, but the research tended to work with really high doses and looked for obvious toxicity like cell death. The current study looked at cell function which is a more subtle effect and looked at nonparticle doses which are closer to what might people might really be exposed to.

The nanoparticles tend to settle onto the cells representing the gastrointestinal tract and cause loss or remodeling of the microvilli which are tiny projections on the surface of the intestinal absorptive cells that assist in increasing the surface area available for absorption. Loss of surface area tends to result in a decrease in nutrient absorption. Also, some of the nanoparticles cause pro-inflammatory signaling at high doses which can increase the permeability of the intestinal model. An increase in intestinal permeability means that compounds that are not supposed to pass through into the bloodstream might be able to.

The researchers note that it is difficult to forecast what the long-term effects of nanoparticle ingestion are on human health, especially based on results from a cell culture model. The model does show that the nanoparticles do have effects on the in vitro model, and understanding their effect on the gut function is an important area of study for consumer safety. Future studies will focus on the food additive-gut microbiome interactions.

Journal Reference:
1. Fabiola Moreno-Olivas, Elad Tako, Gretchen J. Mahler. ZnO nanoparticles affect intestinal function in an in vitro model. Food & Function, 2018; 9 (3): 1475 DOI: 10.1039/C7FO02038D

Study Proves Older People Can Generate New Brain Cells

Brain Cells

Researchers show for the first time that healthy older men and women can generate just as many new brain cells as younger people.

There has been controversy over whether adult humans grow new neurons, and some research has previously suggested that the adult brain was hard-wired and that adults did not grow new neurons. This study, to appear in the journal Cell Stem Cell on April 5, counters that notion. Lead author Maura Boldrini, associate professor of neurobiology at Columbia University, says the findings may suggest that many senior citizens remain more cognitively and emotionally intact than commonly believed.

“We found that older people have similar ability to make thousands of hippocampal new neurons from progenitor cells as younger people do,” Boldrini says. “We also found equivalent volumes of the hippocampus (a brain structure used for emotion and cognition) across ages. Nevertheless, older individuals had less vascularization and maybe less ability of new neurons to make connections.”

The researchers tested hippocampi from 28 previously healthy individuals aged 14-79. This is the first time researchers looked at newly formed neurons and the state of blood vessels within the entire human hippocampus. The researchers had determined that study subjects were not cognitively impaired and had not suffered from depression or taken antidepressants, which Boldrini and colleagues had previously found could impact the production of new brain cells.

In rodents and primates, the ability to generate new hippocampal cells declines with age. Waning production of neurons and an overall shrinking of the dentate gyrus, part of the hippocampus thought to help form new episodic memories, was believed to occur in aging humans as well.

The researchers from Columbia University and New York State Psychiatric Institute found that even the oldest brains they studied produced new brain cells. “We found similar numbers of intermediate neural progenitors and thousands of immature neurons,” they wrote. Nevertheless, older individuals form fewer new blood vessels within brain structures and possess a smaller pool of progenitor cells descendants of stem cells that are more constrained in their capacity to differentiate and self-renew.

Boldrini surmised that reduced cognitive-emotional resilience in old age may be caused by this smaller pool of neural stem cells, the decline in vascularization, and reduced cell-to-cell connectivity within the hippocampus. “It is possible that ongoing hippocampal neurogenesis sustains human-specific cognitive function throughout life and that declines may be linked to compromised cognitive-emotional resilience,” she says.

Boldrini says that future research on the aging brain will continue to explore how neural cell proliferation, maturation, and survival are regulated by hormones, transcription factors, and other inter-cellular pathways.

Reference: Maura Boldrini, Camille A. Fulmore, Alexandria N. Tartt, Laika R. Simeon, Ina Pavlova, Verica Poposka, Gorazd B. Rosoklija, Aleksandar Stankov, Victoria Arango, Andrew J. Dwork, Ren? Hen, J. John Mann. Human Hippocampal Neurogenesis Persists throughout Aging. Cell Stem Cell, 2018; 22 (4): 589 DOI: 10.1016/j.stem.2018.03.015

A New Way to Measure the Biological Age of Cells

Biological Age

A study published in Nature Genetics and led by scientists at Van Andel Research Institute (VARI) and Cedars Sinai, have developed a new computational, straightforward method to measure cellular age. The findings may lead to simpler, better screening and a way to measure the success of anti-aging therapies.

The findings reveal a measurable, progressive loss of specific chemical tags that regulate gene activity and can be detected at the earliest stays of development. These changes will continue throughout a person?s life and will correlate with cellular rather than chronological age.

The study builds on a 2011 long time collaboration and discovery by Benjamin Berman, Ph. D. of Cedars-Sinai and Peter Laird, Ph.D. and Hui Shen, Ph.D. of VARI. The 2011 discovery first determined loss of these DNA marks (called methyl groups) occurs in specific areas of the genome. However, at the time the techniques used could not detect this process occurring in normal cells. Our cellular clock begins ticking the moment our cells start dividing. This method allowed the researchers to track the history of the past divisions and measure age-related changes to the genetic code that may contribute to both dysfunction and normal aging.

Every cell in the nearly 40 trillion cells in the human body can trace its lineage back to a single, fertilized egg cell which contains the original copy of a person?s DNA. Throughout a person?s lifetime, the cells divide and replace damaged or old cells at different rates based on factors such as their function in the body, would healing and environmental insults.

Even though undergoing elaborate biological quality control checks, each cell division chips away at the genome?s integrity which leaves behind an accumulating number of changes. Principal among these is a dramatic shift in the location and number of methyl groups on the genome which is part of a process that begins during fetal development and continues through a lifetime.

What the researchers found striking about the results from their new method is that they push back the start of that process to the earliest stages of in utero development. Until recently mechanisms behind loss of DNA methyl groups (known as hypomethylation) have largely been unknown. It appears to be more profound in tissues with a high turnover rate such as skin and the epithelium. Typically, tissues with high turnover rates are more susceptible because there are more chances for errors to accumulate. What is being seen is a normal process of cellular aging.

The research project encompassed more than 200 mouse datasets and 340 human datasets the most in-depth study of its kind. The study would not have been possible without massive swaths of accessible data from large-scale sequencing projects.

Reference: Wanding Zhou, Huy Q. Dinh, Zachary Ramjan, Daniel J. Weisenberger, Charles M. Nicolet, Hui Shen, Peter W. Laird, Benjamin P. Berman. DNA methylation loss in late-replicating domains is linked to mitotic cell division. Nature Genetics, 2018; DOI: 10.1038/s41588-018-0073-4