lroot on February 21st, 2018

Monosaturared Fatty Acid Foods

A study conducted at the University of Illinois has revealed that monounsaturated fatty acids (MUFAs) which are a class of nutrients found in nuts, avocados and olive oils are linked to general intelligence. Additionally they discovered that this relationship is driven by the correlation of MUFAs and the organization of the brain’s attention network. Researchers know that nutrition is linked to cognitive performance, however they had not previously pinpointed what underlies the connection.

The study published in the Nuerolmage Journal, involved 99 healthy older adults. It compared the patterns of fatty acid nutrients found in blood samples, functional MRI data which measured the efficiency of the brain networks and the results of a general intelligence test. The goal was to better understand how nutrition could be used to support cognitive performance and to study ways in which nutrition might also influence functional organization of the brain.

The researchers studied the relationship between groups of fatty acids and brain networks which underlie general intelligence. The goal was to understand whether the brain network organization mediated the relationship between general intelligence and fatty acids. Researchers were inspired by previous studies suggesting cognitive benefits of the Mediterranean diet which is naturally rich in MUFAs. Nutrients in the participants blood were examined and researchers found that the fatty acids clustered into saturated fatty acids and monounsaturated fatty acids. Rather than focusing on single nutrients, the researchers wanted to focus on broader dietary patterns.

The study revealed that general intelligence was associated with the brains dorsal attention network which plays a key role in everyday problem solving and attention-demanding tasks. The scientists found that general intelligence was associated with how efficiently the dorsal attention network is functionally organized using a measure called small-world propensity which describes how efficiently the neural network is connected within locally clustered regions as well as across globally integrated systems.

What they found was participants with higher levels of MUFAs in their blood had greater small-world propensity in their dorsal attention network. Taken together with an observed correlation between higher levels of MUFAs and greater general intelligence the findings suggest a pathway by which MUFAs affect cognition. The findings provide novel evidence that MUFAs are related to the dorsal attention network and how optimal this network is functionally organized. The results suggest that the dorsal attention network must be taken into consideration when understanding the relationship between MUFAs and general intelligence. It is part of the underlying mechanism that contributes to the relationship.

The hope is these findings will guide additional research into how nutrition affects intelligence and cognition. Further studies would involve an interventional study over time to see whether long-term MUFA intake influences brain network intelligence and organization. The evidence can certainly motivate promising new directions for future research in nutritional cognitive neuroscience.

Reference: Marta K. Zamroziewicz, M. Tanveer Talukdar, Chris E. Zwilling, Aron K. Barbey. Nutritional status, brain network organization, and general intelligence. NeuroImage, 2017; 161: 241 DOI: 10.1016/j.neuroimage.2017.08.043

Fast FoodA recent study by a team at the Institute for Innate Immunity of the University of Bonn has discovered even more negative consequences as the result of a diet of fast food. Unhealthy food with a diet high in unhealthy fat and calories makes the body’s immune defenses aggressive even after switching to a healthy diet. The immune system reacts to this type of diet in a similar manner as it does to a bacterial infection. All of which leads to disease and other negative health ramifications.

The scientists put mice on a “Western” Diet for one month. The diet was high in fat, high in sugar and low in fiber. The mice developed a strong inflammatory response throughout the body similar to symptoms with an infection with dangerous bacteria. The unhealthy diet resulted in an unexpected increase in the number of immune cells in the blood of the mice especially monocytes and granulocytes which help fight off bacteria, viruses and fungi. This indicated the involvement of immune cell progenitors in the bone marrow. To further understand these findings, bone marrow progenitors for major immune cell types were isolated from the mice fed a Western Diet and mice fed a healthy controlled diet. Genomic studies indicated the mice receiving the Western Diet did activate a large number of genes in the progenitor cells, genes responsible for proliferation and maturation. Findings indicate that fast food causes the body to very quickly recruit a powerful and huge army. When the mice were put back on their typical diet of cereal for another four weeks, the acute inflammation disappeared. However, what did not disappear was the genetic reprogramming of the immune cells and their precursors. Even after this length of time, the genes that had been turned on during the fast food diet were still active.

Only recently has it been discovered that the innate immune system has a form of memory. Following an infection, the body’s defenses remain in an alert state called “innate immune training”. This allows the body’s defenses to respond more quickly to a new attack. In the mice, this process was triggered by an unhealthy diet rather than bacterium.

The scientists then examined the blood cells from 120 subjects. They identified the responsible “fast food sensor” in immune cells. In some of the subjects, the innate immune system showed a strong training effect with researchers discovering genetic evidence of the involvement of a so-called inflammasomes. Inflammasomes are key intracellular signaling complexes which recognize infectious agents and other harmful substances which subsequently release highly inflammatory messages. In addition to the inflammatory response, this also has long-term consequences for the immune system’s responses. The Western diet changes the way in which genetic information is packaged.

This genetic material is stored in the DNA with each cell containing several DNA strands. They are typically wrapped around certain proteins in the nucleus and therefore many genes in the DNA cannot be read as they are too inaccessible. An unhealthy diet causes some of the normally hidden pieces of DNA to unwind and this area of the genetic material can be read much easier as long as the temporary unwrapping remains active. The inflammasomes trigger epigenetic changes and the immune system consequently reacts to even small stimuli with stronger inflammatory responses. This inflammatory response then accelerates the development of a variety of diseases and contributes to the growth of lipids and immune cells which will migrate to altered vessel walls which may result in serious health consequences.

These findings have important societal relevance. In recent centuries the average life expectancy has steadily increased in Western countries. That trend is currently being broken for the first time with individuals born today living an average shorter life than their parents. Too little exercise and unhealthy diets play a decisive role. The researchers strongly emphasize a healthy diet as the foundation for developing early habits that can affect long-term health.

Journal Reference: Anette Christ, Patrick Günther, Mario A.R. Lauterbach, Peter Duewell, Debjani Biswas, Karin Pelka, Claus J. Scholz, Marije Oosting, Kristian Haendler, Kevin Baßler, Kathrin Klee, Jonas Schulte-Schrepping, Thomas Ulas, Simone J.C.F.M. Moorlag, Vinod Kumar, Min Hi Park, Leo A.B. Joosten, Laszlo A. Groh, Niels P. Riksen, Terje Espevik, Andreas Schlitzer, Yang Li, Michael L. Fitzgerald, Mihai G. Netea, Joachim L. Schultze, Eicke Latz. Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming. Cell, 2018; 172 (1-2): 162 DOI: 10.1016/j.cell.2017.12.013

lroot on February 8th, 2018


New research has shown evidence and interactions between psychological and physical health effects that involve mitochondria according to experimental studies conducted by Martin Picard of Columbia University and Bruce S. McEwen of The Rockefeller University. Mitochondria are specialized cellular structures with their own DNA and are found in nearly every type of cell in the body. Sometimes referred to as cellular “powerhouses”, they generate signals and energy required for life. When they are not working correctly, they can cause severe diseases affecting many of the different body systems.

A total of 23 experimental studies on animals conducted by researchers around the world points to mitochondria as a potential intersection between psychosocial experiences and biological stress responses. Researchers have found that acute and chronic stress influenced specific aspects of mitochondrial function, especially in the brain. A wide range of factors including genes, diet and behavior may also influence mitochondrial vulnerability to stress. The Doctors have also outlined a conceptual framework by which mitochondria may convert the effects of psychological stress on to physical health. Evidence indicates that mitochondria sense, integrate and signal information about the environment and includes stress induced mediators which cause functional and structural recalibration of the mitochondria.

Describing the functional and structural changes that mitochondria undergo as response to chronic stress, the Doctors introduced the concept of MAL (Mitochondrial Allostatic Load). These changes may lead to widespread health effects such as increased inflammation leading to a higher risk of disease and damage to cellular DNA leading to accelerated aging. It appears that mitochondria is involved in regulating the body’s stress reactivity systems including controlling immunity, inflammation and the brain. Damage to mitochondrial DNA has been associated with a biological aging clock. Recent studies have shown that mitochondria affect the rate of aging in mammals, however it is not clear whether this is the case in humans.

Emerging evidence on the role of mitochondria and translating the effects of stress on physical health extend the reach of mind-body research into the cellular/molecular domain. The findings are particularly exciting for psychosomatic medicine with its focus on reintegrating the mind and body. The findings also represent the core foundation of current biomedical training and practice. The doctors emphasize that more research is needed to test various elements of their model in humans and to further consider the dynamic bi-directional interactions between important physiological systems and mitochondria.

Journal References:

1. Martin Picard, Bruce S. McEwen. Psychological Stress and Mitochondria: A Systematic Review. Psychosomatic Medicine, 2018; 80 (2): 141 DOI: 10.1097/PSY.0000000000000545

2. Martin Picard, Bruce S. McEwen. Psychological Stress and Mitochondria: A Conceptual Framework. Psychosomatic Medicine, 2018; 80 (2): 126 DOI: 10.1097/PSY.0000000000000544


Objective Mitochondria are multifunctional life-sustaining organelles that represent a potential intersection point between psychosocial experiences and biological stress responses. This article provides a systematic review of the effects of psychological stress on mitochondrial structure and function.

Methods: A systematic review of the literature investigating the effects of psychological stress on mitochondrial function was conducted. The review focused on experimentally controlled studies allowing us to draw causal inference about the effect of induced psychological stress on mitochondria.

Results: A total of 23 studies met the inclusion criteria. All studies involved male laboratory animals, and most demonstrated that acute and chronic stressors influenced specific facets of mitochondrial function, particularly within the brain. Nineteen studies showed significant adverse effects of psychological stress on mitochondria and four found increases in function or size after stress. In humans, only six observational studies were available, none with experimental designs, and most only measured biological markers that do not directly reflect mitochondrial function, such as mitochondrial DNA copy number.

Conclusons: Overall, evidence supports the notion that acute and chronic stressors influence various aspects of mitochondrial biology, and that chronic stress exposure can lead to molecular and functional recalibrations among mitochondria. Limitations of current animal and human studies are discussed. Maladaptive mitochondrial changes that characterize this subcellular state of stress are termed mitochondrial allostatic load. Prospective studies with sensitive measures of specific mitochondrial outcomes will be needed to establish the link between psychosocial stressors, emotional states, the resulting neuroendocrine and immune processes, and mitochondrial energetics relevant to mind-body research in humans.

lroot on February 5th, 2018

Dim Light

Spending too much time in dimly lit rooms and offices may actually change the brain’s structure and hurt one’s ability to remember and learn, indicates groundbreaking research by Michigan State University neuroscientists.

The researchers studied the brains of Nile grass rats (which, like humans, are diurnal and sleep at night) after exposing them to dim and bright light for four weeks. The rodents exposed to dim light lost about 30 percent of capacity in the hippocampus, a critical brain region for learning and memory, and performed poorly on a spatial task they had trained on previously.

The rats exposed to bright light, on the other hand, showed significant improvement on the spatial task. Further, when the rodents that had been exposed to dim light were then exposed to bright light for four weeks (after a month-long break), their brain capacity and performance on the task recovered fully.

The study, funded by the National Institutes of Health, is the first to show that changes in environmental light, in a range normally experienced by humans, leads to structural changes in the brain. Americans, on average, spend about 90 percent of their time indoors, according to the Environmental Protection Agency.

“When we exposed the rats to dim light, mimicking the cloudy days of Midwestern winters or typical indoor lighting, the animals showed impairments in spatial learning,” said Antonio “Tony” Nunez, psychology professor and co-investigator on the study. “This is similar to when people can’t find their way back to their cars in a busy parking lot after spending a few hours in a shopping mall or movie theater.”

Nunez collaborated with Lily Yan, associate professor of psychology and principal investigator on the project, and Joel Soler, a doctoral graduate student in psychology. Soler is also lead author of a paper on the findings published in the journal Hippocampus.

Soler said sustained exposure to dim light led to significant reductions in a substance called brain derived neurotrophic factor a peptide that helps maintain healthy connections and neurons in the hippocampus and in dendritic spines, or the connections that allow neurons to “talk” to one another.

“Since there are fewer connections being made, this results in diminished learning and memory performance that is dependent upon the hippocampus,” Soler said. “In other words, dim lights are producing dimwits.”

Interestingly, light does not directly affect the hippocampus, meaning it acts first other sites within the brain after passing through the eyes. Yan said the research team is investigating one potential site in the rodents’ brains a group of neurons in the hypothalamus that produce a peptide called orexin that’s known to influence a variety of brain functions. One of their major research questions: If orexin is given to the rats that are exposed to dim light, will their brains recover without being re-exposed to bright light?

The project could have implications for the elderly and people with glaucoma, retinal degeneration or cognitive impairments.

“For people with eye disease who don’t receive much light, can we directly manipulate this group of neurons in the brain, bypassing the eye, and provide them with the same benefits of bright light exposure?” Yan said. “Another possibility is improving the cognitive function in the aging population and those with neurological disorders. Can we help them recover from the impairment or prevent further decline?”

Reference: Joel E. Soler, Alfred J. Robison, Antonio A. Núñez, Lily Yan. Light modulates hippocampal function and spatial learning in a diurnal rodent species: A study using male nile grass rat (Arvicanthis niloticus). Hippocampus, 2017; DOI: 10.1002/hipo.22822

Dr Bryant Villeponteau the formulator of Stem Cell 100 and other Life Code nutraceuticals was recently interviewed by Dr Mercola who owns the largest health web site on the internet. Dr. Villeponteau is also the author of Decoding Longevity an new book which will be released during December. He is a leading researcher in novel anti-aging therapies involving stem cells an area in which he has been a pioneer for over three decades.

Stem cell technology could have a dramatic influence on our ability to live longer and replace some of our failing parts, which is the inevitable result of the aging process. With an interest in aging and longevity, Dr. Villeponteau started out by studying developmental biology. “If we could understand development, we could understand aging,” he says. Later, his interest turned more toward the gene regulation aspects. While working as a professor at the University of Michigan at the Institute of Gerontology, he received, and accepted, a job offer from Geron Corporation—a Bay Area startup, in the early ‘90s.

“They were working on telomerase, which I was pretty excited about at the time. I joined them when they first started,” he says. “We had an all-out engagement there to clone human telomerase. It had been cloned in other animals but not in humans or mammals.”

If you were to unravel the tip of the chromosome, a telomere is about 15,000 bases long at the moment of conception in the womb. Immediately after conception, your cells begin to divide, and your telomeres begin to shorten each time the cell divides. Once your telomeres have been reduced to about 5,000 bases, you essentially die of old age.

“What you have to know about telomerase is that it’s only on in embryonic cells. In adult cells, it’s totally, for the most part, turned off, with the exception of adult stem cells,” Dr. Villeponteau explains. “Adult stem cells have some telomerase – not full and not like the embryonic stem cells, but they do have some telomerase activity.”

Most of the research currently being done, both in academia and industrial labs, revolves around either embryonic stem cells, or a second type called induced pluripotent stem cells (iPS). Dr. Villeponteau, on the other hand, believes adult stem cells are the easiest and most efficient way to achieve results.

That said, adult stem cells do have their drawbacks. While they’re your own cells, which eliminates the problem of immune-related issues, there’s just not enough of them. Especially as you get older, there are fewer and fewer adult stem cells, and they tend to become increasingly dysfunctional too. Yet another hurdle is that they don’t form the tissues that they need to form…

To solve such issues, Dr. Villeponteau has created a company with the technology and expertise to amplify your adult stem cells a million-fold or more, while still maintaining their ability to differentiate all the different cell types, and without causing the cells to age. Again, it is the adult stem cell’s ability to potentially cure, or at least ameliorate, many of our age-related diseases by regenerating tissue that makes this field so exciting.

Dr Villeponteau believes you can add many years, likely decades, to your life simply by eating right, exercising (which promotes the production of muscle stem cells, by the way) and living an otherwise clean and healthy lifestyle. Extreme life extension, on the other hand, is a different matter.

His book, Decoding Longevity, covers preventive strategies to prolong your life, mainly diet, exercise, and supplements. A portion of the book also covers future developments in the area of more radical life extension, such as stem cell technology.

If you would like to read the entire interview here is a link to the text version:

Transcript of Interview With Dr. Bryant Villeponteau by Dr. Joseph Mercola

lroot on February 1st, 2018

Now researchers have found a way not just to stop, but, reverse the aging process. The key is something called a telomere. We all have them. They are the tips or caps of your chromosomes. They are long and stable in young adults, but, as we age they become shorter, damaged and frayed. When they stop working we start aging and experience things like hearing and memory loss.

In a recent study published in the peer reviewed journal Nature scientists took mice that were prematurely aged to the equivalent of 80-year-old humans, added an enzyme and essentially turned their telomeres back on. After the treatment they were the physiological equivalent of young adults. You can see the before and after pictures in the videos above. Brain function improved, their fertility was restored it was a remarkable reversal of the aging process. In the top video the untreated mouse shows bad skin, gray hair and it is balding. The mouse with it’s telomeres switched back on has a dark coat color, the hair is restored and the coat has a nice healthy sheen to it. Even more dramatic is the change in brain size. Before treatment the aged mice had 75% of a normal size brain like a patient with severe Alzheimers. After the telomeres were reactivated the brain returned to normal size. As for humans while it is just one factor scientists say the longer the telomeres the better the chances for a more graceful aging.

The formal study Telomere dysfunction induces metabolic and mitochondrial compromise was published in Nature.

Additional information published by Harvard can be found in the following articles.

Scientists Find Root Molecular Cause of Declining Health in the Old

Decoding Immortality – Smithsonian Channel Video about the Discovery of Telomerase

While scientists are not yet able to accomplish the same results in humans we believe we have developed a nutraceutical to help prolong youth and possibly extend life until age reversal therapy for humans becomes available.

lroot on January 29th, 2018

New evidence that adult stem cells are critical to human aging has recently been published on a study done on a super-centenarian woman that lived to be 115 years. At death, her circulating stem cell pool had declined to just two active stem cells from stem cell counts that are typically more than a thousand in younger adults. Super-centenarians have survived all the normal diseases that kill 99.9% of us before 100 years of age, so it has been a mystery as to what actually kills these hardy individuals. This recent data suggest that stem cell decline may be the main contributor to aging. If so, stabilizing stem cells may be the best thing one can do to slow your rate of aging.

There are many theories of aging that have been proposed. For example, damage to cells and tissues from oxidative stress has been one of the most popular fundamental theories of aging for more than half a century. Yet antioxidant substances or genes that code antioxidant enzymes have proven largely ineffective in slowing aging when tested in model animals. Thus, interest by scientists has shifted to other hypotheses that might provide a better explanation for the slow declines in function with age.

Stem cells provide one such promising mechanism of aging. Of course, we all know that babies are young and vigorous, independent of the age of their parents. This is because adults have embryonic stem cells that can generate young new cells needed to form a complete young baby. Indeed, these embryonic stem cells are the product of continuously evolving stem cell populations that go back to the beginning of life on earth over 3.5 billion years ago!

In adults, the mostly immortal embryonic stem cells give rise to mortal adult stem cells in all the tissues of the body. These adult stem cells can regenerate your cells and tissues as they wear out and need replacement. Unfortunate, adult stem cells also age, which leads to fewer cells and/or loss of function in cell replacement. As functional stem cells decline, skin and organs decline with age.

Blood from world’s oldest woman suggests life limit

Time Magazine: Long-Life Secrets From The 115-Year-Old Woman

Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis

The somatic mutation burden in healthy white blood cells (WBCs) is not well known. Based on deep whole-genome sequencing, we estimate that approximately 450 somatic mutations accumulated in the nonrepetitive genome within the healthy blood compartment of a 115-yr-old woman. The detected mutations appear to have been harmless passenger mutations: They were enriched in noncoding, AT-rich regions that are not evolutionarily conserved, and they were depleted for genomic elements where mutations might have favorable or adverse effects on cellular fitness, such as regions with actively transcribed genes. The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages.

lroot on January 22nd, 2018

Adult Stem Cells

New research by a team at the University of South Carolina has discovered a way to increase the body’s ability to heal after injury. The study led by Assistant Professor of Stem Cell Biology and Regenerative Medicine, has proved that adult stem cells will enter an alert state when the body sustains an injury. These “alerted” stem cells have a greater ability to repair and heal damaged tissues.

It is theorized that after an injury a person’s blood can produce a state of alert. Using lab mice, the researchers injected healthy mice with blood from their injured counterparts. The stem cells in the healthy mice went into a state of alert. The team then identified the enzyme Hepatocyte Growth Factor Activator (HGFA), as the chemical mechanism that signaled cells to an alert state. HGFA is always in the bloodstream but only activates when the body experiences an injury. The enzyme signals adult stem cells to enter this state of alert once an injury occurs.

The team then decided to see what would happen if an injury occurred while the adult stem cells were already in a state of alert. Healthy mice were injected with HGFA. A few days later the mice were given muscle and skin injuries. The test mice were observed to heal faster, regrow missing fur and after just nine days returned to running on exercise wheels sooner. Twenty days after the injuries, the mice that had been injected with HGFA had regenerated larger muscle fibers compared to the untreated mice.

The findings support the idea that the presence of HGFA in the bloodstream prepares the body to respond faster and more efficiently to an injury. The response was similar to how vaccines prepare the body to fight specific diseases. HGFA prepares the cells to respond to tissue damage. By “priming” the body, you can speed the process of tissue repair and recovery.

It is hoped that in the future people may be able to use HGFA prior to engaging in activities that might result in injury including sports, surgery and even combat. HGFA may also be able to be used therapeutically for people with compromised healing abilities. And this therapeutic approach may also be of value for the elderly. As we age, the body’s ability to heal itself slows down as stem cell activity diminishes with advancing age. The team posed the concept that it might be possible to restore youthful healing by activating the HGFA pathway!

Reference: Joseph T. Rodgers, Matthew D. Schroeder, Chanthia Ma, Thomas A. Rando. HGFA Is an Injury-Regulated Systemic Factor that Induces the Transition of Stem Cells into GAlert. Cell Reports, April 2017 DOI: 10.1016/j.celrep.2017.03.066

lroot on January 18th, 2018

Stem Cell Gene Activation

In a scientific first, researchers at the Gladstone Institutes turned skin cells from mice into stem cells by activating a specific gene in the cells using CRISPR technology. The innovative approach offers a potentially simpler technique to produce the valuable cell type and provides important insights into the cellular reprogramming process.

“This is a new way to make induced pluripotent stem cells that is fundamentally different from how they’ve been created before,” said author Sheng Ding, PhD, a senior investigator at Gladstone. “At the beginning of the study, we didn’t think this would work, but we wanted to at least try to answer the question: can you reprogram a cell just by unlocking a specific location of the genome? And the answer is yes.”

Pluripotent stem cells can be turned into virtually any cell type in the body. As a result, they are a key therapeutic resource for currently incurable conditions, such as heart failure, Parkinson’s disease, and blindness. They also provide excellent models to study diseases and important tools to test new drugs in human cells.

In 2006, Gladstone Senior Investigator Shinya Yamanaka, MD, PhD, discovered he could make stem cells — dubbed induced pluripotent stem cells (iPSCs) — by treating ordinary skin cells with four key proteins. These proteins, called transcription factors, work by changing which genes are expressed in the cell, turning off genes associated with skin cells and turning on genes associated with stem cells.

Building on this work, Ding and others previously created iPSCs not with transcription factors, but by adding a cocktail of chemicals to the cells. The latest study, published in Cell Stem Cell, offers a third way to turn skin cells into stem cells by directly manipulating the cells’ genome using CRISPR gene regulation techniques.

“Having different options to make iPSCs will be useful when scientists encounter challenges or difficulties with one approach,” said Ding, who is also a professor of pharmaceutical chemistry at the University of California, San Francisco. “Our approach could lead to a simpler method of creating iPSCs or could be used to directly reprogram skin cells into other cell types, such as heart cells or brain cells.”

CRISPR is a powerful tool that can precisely manipulate the genome by targeting a unique sequence of DNA. That sequence of DNA is then either permanently deleted or replaced, or it is temporarily turned on or off.

Ding’s team targeted two genes that are only expressed in stem cells and known to be integral to pluripotency: Sox2 and Oct4. Like transcription factors, these genes turn on other stem cell genes and turn off those associated with different cell types.

The researchers discovered that with CRISPR, they could activate either Sox2 or Oct4 to reprogram cells. In fact, they showed that targeting a single location on the genome was enough to trigger the natural chain reaction that led to reprogramming the cell into an iPSC.

For comparison, four transcription factors are typically used to create iPSCs using the original method. What’s more, one transcription factor typically targets thousands of genomic locations in the cell and changes gene expression at each location.

“The fact that modulating one site is sufficient is very surprising,” said Ding. “Now, we want to understand how this whole process spreads from a single location to the entire genome.”

Reference: Peng Liu, Meng Chen, Yanxia Liu, Lei S. Qi, Sheng Ding. CRISPR-Based Chromatin Remodeling of the Endogenous Oct4 or Sox2 Locus Enables Reprogramming to Pluripotency. Cell Stem Cell, 2018; DOI: 10.1016/j.stem.2017.12.001

Abstract: Generation of induced pluripotent stem cells typically requires the ectopic expression of transcription factors to reactivate the pluripotency network. However, it remains largely unclear what remodeling events on endogenous chromatin trigger reprogramming toward induced pluripotent stem cells (iPSCs). Toward this end, we employed CRISPR activation to precisely target and remodel endogenous gene loci of Oct4 and Sox2. Interestingly, we found that single-locus targeting of Sox2 was sufficient to remodel and activate Sox2, which was followed by the induction of other pluripotent genes and establishment of the pluripotency network. Simultaneous remodeling of the Oct4 promoter and enhancer also triggered reprogramming. Authentic pluripotent cell lines were established in both cases. Finally, we showed that targeted manipulation of histone acetylation at the Oct4 gene locus could also initiate reprogramming. Our study generated authentic iPSCs with CRISPR activation through precise epigenetic remodeling of endogenous loci and shed light on how targeted chromatin remodeling triggers pluripotency induction.

lroot on January 18th, 2018


A good night’s sleep makes an important contribution to our health while a poor night’s sleep has a negative effect. A new study published in the Nature Communications Journal by the University of Zurich and the Swiss Federal Institute of Technology in Zurich has discovered there is a connection between deep sleep and learning efficiency.

The researchers set out to examine how disturbed deep sleep affects the brain’s ability to learn new things. More specifically, the researchers were interested in the brain’s ability to adapt and change in response to stimuli received from the environment in the motor cortex and how it is affected by deep sleep. The motor cortex is the part of the brain that is responsible for controlling and developing motor skills. The deep sleep phase, also referred to as the slow-wave sleep phase, is key to memory processing and formation and additionally helps the brain restore itself after daytime activity.

The study included seven men and six women. All were asked to perform motoric tasks during the day followed by a night of undisturbed sleep followed by a night during which time their deep sleep was disturbed. The daytime tasks involved a variety of finger movements, and the researchers identified precisely the area of the brain responsible for learning movements. Using an electroencephalogram, the researchers monitored the brain activity while the participants slept.

On the first night following the first session of learning movements, the participants were able to sleep without disturbances. During the second night of the study, the researchers manipulated the quality of sleep. They focused on the motor cortex while disrupting deep sleep therefore studying the impact poor, disturbed sleep has on the neuroplasticity associated with practicing new movements. None of the participants knew their deep sleep was being tampered with. To them, quality of sleep was identical both nights.

Researchers then studied each participant’s ability to learn new movements. The participants learning performance was at its highest in the morning as expected. However, as the day progressed, more and more mistakes were made which again was as expected.
What the researchers found after a restorative night’s sleep was the participants learning efficiency spiked again. However, following the night of disturbed, manipulative sleep, the learning efficiency did not improve as significantly and the participant’s performance was as low in the morning as it was on the evening of the previous day.

According to the researchers, during manipulated deep sleep the neuron’s synapses did not rest which would normally occur during deep sleep. Our synapses get excited during the day as response to a variety of stimuli throughout each day. With sleep, these synapses restore themselves and activity normalizes. Without a restorative period of time, the synapses stay maximally excited for too long a period. This state inhibits neuroplasticity which means learning new things is no longer possible. Learning efficiency was saturated in the strongly excited area of the brain which inhibited learning new motor skills.

To further ensure they had located the right area of the brain responsible for deep sleep, the researchers conducted the experiment again this time assigning the same tasks as in the first study, but this time manipulated a different region of the brain. There was no change in the results of the participant’s performance.

The study revealed that poor sleep keeps the brain’s synapses excited by blocking the brain’s ability to learn. This is the first study to reveal the connection between deep sleep and learning efficiency. According to Reto Huber, Professor at the University Children’s Hospital in Zurich, the significance of the study also helped provide valuable information and insight into many diseases that manifest in sleep as well. The hope is that specific areas of the brain associated with a variety of diseases can be manipulated.

Reference: Sara Fattinger, Toon T. de Beukelaar, Kathy L. Ruddy, Nicole Wenderoth, Reto Huber; Deep sleep maintains learning efficiency of the human brain. Nat. Commun. 8, 15405 doi: 10.1038/ncomms15405 (2017)