Plant germ cells also go through methylation reprogramming

Plant germ cells also go through methylation reprogramming - and functionally it is essential


Excerpt: "A new study has revealed an undiscovered reprogramming mechanism that allows plants to maintain fitness down the generations.

The John Innes Centre team led by Dr Xiaoqi Feng made the discovery when studying germ cells - cells specialised for sexual reproduction - in flowering plants.

Germ cells are often referred to as “immortal” because they can pass their genetic material through the generations. They have been the subject of much scientific scrutiny.

This study aimed to solve a long-term debate on whether the germ cells in plants undergo an event of DNA methylation reprogramming at each reproductive cycle.

DNA methylation is a modification of DNA, which changes the activity of DNA without changing the genetic sequence.

It is a cornerstone epi-genetics – one of the fastest growing fields in life sciences with potential to deliver improvements in human and plant health.

DNA methylation reprogramming - known to exist in animals – occurs most dramatically in germ cells and regulates the reproductive success from generation to generation. Published in Nature Genetics the JIC team worked in collaboration with colleagues from the University of Leicester to reveal for the first time the existence of DNA methylation changes in the germline of flowering plants.

They also reveal the mechanism by which this reprogramming happens - via a process known as de novo (anew) DNA methylation and its biological significance in maintaining reproductive success.

Dr Feng, project leader at the John Innes Centre, explains: “We knew this DNA methylation re-setting is extensive and important in animals where methylation is erased and re-established between generations.

“But because plants carry DNA methylation information really well through generations, it was believed there was not much methylation reprogramming going on in plant germ cells. What we have discovered shows plant germ cells also go through methylation reprogramming and functionally it is essential.”

The John Innes Centre team made the discovery while applying genetic analysis to male sexual lineage in the reference plant Arabidopsis thaliana.

The research funded by BBSRC is a key breakthrough in fundamental understanding of epigenetic regulation of plant development.

Dr. Feng explained “Our research shows that developmentally regulated DNA methylation reprogramming can regulate plant development. Scientists have been searching for this for a long time. We show that genes can be regulated in specific cells via the de novo DNA methylation pathway, which is prevalent in many plant tissues, hence this mechanism may apply to many processes in plants.”
“Understanding how this naturally occurs during plant development is the first step in understanding how specific genes can be targeted by this epigenetic modification and hence regulated.

Additionally, understanding how DNA methylation is inherited through the germ cells is essential for understanding the transgenerational stability of incurred methylation changes. Both are essential to harness epigenetics for crop improvement.”"

My comment: Epigenetic reprogramming, like any kind of programming, points to Intelligent Design and Creation. DNA methylation patterns are erased during stages of reproduction and re-constituted by several clever and complex RNA-directed mechanisms. This is done for the organism to be able to efficiently adapt for changing environment. To observe epigenetic reprogramming occurring within plants, tells us about common design, not common ancestor because there is no mechanism for any kind of evolution. Information for the cellular differentiation and epigenetic reprogramming is given by the parents of an organism. The theory of evolution is the major heresy of our time. Don't get lost.


An epigenetic seesaw mechanism works like an analog regulator

An epigenetic seesaw mechanism works like an analog regulator


Excerpt from abstract: "


DNA methylation at promoters is largely correlated with inhibition of gene expression. However, the role of DNA methylation at enhancers is not fully understood, although a crosstalk with chromatin marks is expected. Actually, there exist contradictory reports about positive and negative correlations between DNA methylation and H3K4me1, a chromatin hallmark of enhancers.


We investigated the relationship between DNA methylation and active chromatin marks through genome-wide correlations, and found anti-correlation between H3K4me1 and H3K4me3 enrichment at low and intermediate DNA methylation loci. We hypothesized “seesaw” dynamics between H3K4me1 and H3K4me3 in the low and intermediate DNA methylation range, in which DNA methylation discriminates between enhancers and promoters, marked by H3K4me1 and H3K4me3, respectively. Low methylated regions are H3K4me3 enriched, while those with intermediate DNA methylation levels are progressively H3K4me1 enriched. Additionally, the enrichment of H3K27ac, distinguishing active from primed enhancers, follows a plateau in the lower range of the intermediate DNA methylation level, corresponding to active enhancers, and decreases linearly in the higher range of the intermediate DNA methylation. Thus, the decrease of the DNA methylation switches smoothly the state of the enhancers from a primed to an active state. We summarize these observations into a rule of thumb of one-out-of-three methylation marks: “In each genomic region only one out of these three methylation marks {DNA methylation, H3K4me1, H3K4me3} is high. If it is the DNA methylation, the region is inactive. If it is H3K4me1, the region is an enhancer, and if it is H3K4me3, the region is a promoter”. To test our model, we used available genome-wide datasets of H3K4 methyltransferases knockouts. Our analysis suggests that CXXC proteins, as readers of non-methylated CpGs would regulate the “seesaw” mechanism that focuses H3K4me3 to unmethylated sites, while being repulsed from H3K4me1 decorated enhancers and CpG island shores.


Our results show that DNA methylation discriminates promoters from enhancers through H3K4me1-H3K4me3 seesaw mechanism, and suggest its possible function in the inheritance of chromatin marks after cell division. Our analyses suggest aberrant formation of promoter-like regions and ectopic transcription of hypomethylated regions of DNA. Such mechanism process can have important implications in biological process in where it has been reported abnormal DNA methylation status such as cancer and aging.


...different cells of a population can have different chromatin marks at the same genomic region, and such marks are dynamically changed through the enzymatic activity of methylases and demethylases. Therefore, we use the term “seesaw” rather than “mutual exclusion” to define such mechanism, which includes a balanced state with both marks enriched at lower levels."

My comment: 
DNA methylation regulates discrimination of enhancers from promoters through two different histone marker sets. Enhancers and promoters are widely used by the cell in a mechanism called alternative splicing, which makes it possible for the cell to produce thousands of different proteins based just on one multifunctional gene. DNA methylation patterns are typically affected by diet type, climate, stress etc. which means that these clever mechanisms help organisms go through their ecological adaptation processes. The seesaw mechanism provides a balanced state between two analog type regulatory functions. The interaction between several genomic elements points to Design and Creation. There are no mechanisms for evolution because any change in organisms is based on epigenetic regulation of existing biological information OR loss of it. Don't get lost.


Evolutionary biologists are surprised - Mice are able to see colors

Evolutionary biologists are surprised - Mice are able to see colors


Excerpt from abstract:"

The M5 Cell: A Color-Opponent Intrinsically Photosensitive Retinal Ganglion Cell


•M5 cells are a morphologically and functionally distinct unique ipRGC type
•They have both melanopsin responses and chromatically opponent cone-based signals
•They receive color-opponent signal (UV-ON, green-OFF) via Types 6–9 bipolar cells
•M5 cells innervate the dorsal lateral geniculate nucleus (dLGN)


Intrinsically photosensitive retinal ganglion cells (ipRGCs) combine direct photosensitivity through melanopsin with synaptically mediated drive from classical photoreceptors through bipolar-cell input. Here, we sought to provide a fuller description of the least understood ipRGC type, the M5 cell, and discovered a distinctive functional characteristic—chromatic opponency (ultraviolet excitatory, green inhibitory). Serial electron microscopic reconstructions revealed that M5 cells receive selective UV-opsin drive from Type 9 cone bipolar cells but also mixed cone signals from bipolar Types 6, 7, and 8. Recordings suggest that both excitation and inhibition are driven by the ON channel and that chromatic opponency results from M-cone-driven surround inhibition mediated by wide-field spiking GABAergic amacrine cells. We show that M5 cells send axons to the dLGN and are thus positioned to provide chromatic signals to visual cortex. These findings underscore that melanopsin’s influence extends beyond unconscious reflex functions to encompass cortical vision, perhaps including the perception of color." 

My comment: Several mammals have been thought to be color blind or at least limited with color vision. Evolutionary biologists have believed that only the so-called "more evolved" mammals have the ability to see the colors. A typical argument of evolutionists has also been that the color vision would have evolved due to couple of random, lucky mutations. A recent study shows that evolutionists have once again been wrong. Mice are able to see the colors and the mechanism for seeing the colors is much more complicated than has hitherto been understood. 

The claims of development of color vision are pseudoscientific nonsense, like any other claim that genetic mutations and selection would result in the growth of structural or functional complexity. The Evolutionary theory is the most serious heresy of our time.


lncRNAs might function as barcodes for identifying genomic addresses for maintaining cellular states

lncRNAs might function as barcodes for identifying genomic addresses for maintaining cellular states


Excerpt:"Long noncoding RNAs (lncRNAs) have been implicated in diverse biological processes, including embryonic stem cell (ESC) maintenance. However, their functional mechanisms remain largely undefined. Here, researchers from TU Dresden show that the lncRNA Panct1 regulates the transient recruitment of a putative X-chromosome-encoded protein transient octamer binding factor 1 (TOBF1), to genomic sites resembling the canonical Oct-Sox motif. TOBF1 physically interacts with Panct1 and exhibits a cell-cycle-specific punctate localization in ESCs. At the chromatin level, this correlates with its recruitment to promoters of pluripotency genes. Strikingly, mutating an octamer-like motif in Panct1 RNA abrogates the strength of TOBF1 localization and recruitment to its targets. Taken together, these data reveal a tightly controlled spatial and temporal pattern of lncRNA-mediated gene regulation in a cell-cycle-dependent manner and suggest that lncRNAs might function as barcodes for identifying genomic addresses for maintaining cellular states."

My comment: Barcoding and addressing system together point to Intelligent design and Creation. The role of lncRNAs is very important especially during embryonic development, when lncRNAs transmit the necessary information for the cellular differentiation procedure. There are over a hundred of different types of epigenetic markers that these long non coding RNA molecules carry for establishing the histone coding system, a biological database which determines almost all traits of an organism.
For the theory of evolution these lncRNAs are very truth revealing molecules. For example, the similarity of human/pig lncRNA transcripts is 57% as the corresponding number between humans and chimps is only 29.8%.


"Finally, a large number of pig lncRNAs appeared to have human homologs (57% of total identified lncRNAs) illustrating the similarities between humans and pigs at the genome level."


"The learned transcript similarity threshold for each pair of comparing species varied as a function of distance between species: the empirical threshold for calling a significant human-chimp alignment was 29.8 % sequence similarity."


Cellular programming by 3D folding of the DNA

Cellular programming by 3D folding of the DNA - Incredibly complex mechanism behind the cell differentiation


Excerpt: "During differentiation of pluripotent stem cells to cardiomyocytes, the three-dimensional folding of the DNA reorganizes itself. This reorganization of the DNA architecture precedes and defines important epigenetic patterns. A team lead by private lecturer Dr. Ralf Gilsbach and Stephan Nothjunge, who both conduct research at the University of Freiburg in the Department of Experimental and Clinical Pharmacology and Toxicology headed by Prof. Dr. Lutz Hein, have come to this conclusion. The results suggest that the genome's spatial organization is an important switch for defining cell types, thereby representing a very promising starting point for future reprogramming strategies. The team recently published its results in the scientific journal Nature Communications.

The genome stores information about an organisms development. Each cell carries this information tightly packed on a two-meter long DNA strand in the cell nucleus and specific epigenetic mechanisms control access to the 'blueprint of life'. Because every cell type in a mammalian organism requires access to genomic areas in a tempo-spatial specific manner, the epigenome is crucial for determining cellular identity. It is already known that various epigenetic mechanisms are associated with cell differentiation. Particularly indispensable is the methylation of DNA, in which methyl groups are attached to specific nucleotides of double-stranded DNA. Recent studies also show that differentiation processes are accompanied by a reorganization of the three-dimensional folding of the DNA. Up until now, however, it has been unclear what comes first during cardiomyocyte differentiation: the reorganization of the DNA's folding in the cellular nucleus or the DNA's methylation - and whether these mechanisms are dependent on one another.

In order to address this question, the team lead by the Freiburg pharmacologists used modern sequencing methods. These made it possible to map the three-dimensional genome organization as well as epigenetic mechanisms during the differentiation of cardiomyocytes across the entire genome. For this purpose, the researchers established methods for isolating cardiomyocytes in various developmental stages from healthy mouse hearts. This cell-type-specific analysis was essential to demonstrate that there is a close interplay between epigenetic mechanisms and the spatial folding of the DNA in the cardiomyocytes' nucleus. The comparison of different stages of development showed that the type of spatial folding of DNA defines which methylation patterns are formed and which genes are activated. The researchers proved that the spatial arrangement of the DNA is not dependent on the DNA methylation with cells, among other things, that have no DNA methylation at all. The three-dimensional genome organization is thus a central switchboard for determining cellular identity. In the future, the researchers want to use this switch to control cellular functions."

My comment: Are human programmers able to use 3D folding as a regulator of sub-program activity? I have not heard about such intelligent way of coding. Can you see how perfectly controlled the epigenetic programming for the cellular differentiation is? It has nothing to do with random mutations or selection. These sophisticated mechanisms point to Design and Creation. Don't get lost.


Due to Rapid Human DNA Degradation Rare Diseases Are Increasing in Frequency

Due to Rapid Human DNA Degradation Rare Diseases Are Increasing in Frequency


Human DNA is rapidly degrading. The article below puts quite a bit of figures on the table. As a result of genetic deterioration, there is a huge spectrum of rare genetic diseases. These are not weeded out from the population by any kind of selection, but as the article says, the number of rare diseases is rapidly growing.

By 2020, about 10% of people will carry at least one disease-causing genetic mutation. In Europe, this is about 42 million people, over 400 million in Asia and some 52 million in North America. There are so many diseases caused by genetic mutations that the medical industry is not able to handle them all. When a certain genetic disease is affected by a relatively small proportion of the population, pharmaceutical companies are not economically viable to develop treatment for rare illness. This causes problems for society.

The total number of disease-causing genetic mutations in the human DNA at population level is 214,158. Annual increase was more than 20,000.


According to the Nature's study, about 73% of mutations in human DNA have occurred during the last 5,000 years. All these scientific facts confirm that evolutionary theory is the most serious heresy of our time and that man has not been wandering for many thousands of years on this planet.



Mechanisms behind the cell differentiation

The sophisticated mechanisms behind the cell differentiation reveal the fallacies of the evolutionary theory

There are at least 37 trillion cells in a human body. They can roughly be classified into two hundred cell types that our body needs for different tissue types to produce the necessary proteins and to handle several, e.g. metabolism related tasks. All of our cells have exactly the same DNA sequences (only brain neurons and T cells controlled by the immune defense system make an exception). How does the cell differentiation occur? Why does the skin cell have a completely different identity than a bone cell? Both have exactly the same DNA, so it is clear that the DNA sequences do not determine the task or function of the cell.

Differentiation of the cells begins already during embryonic development. The process is called epigenetic reprogramming. If all of the epigenetic markers on the DNA are wiped out of the cell, it becomes a pluripotent stem cell capable of differentiating into any task. During the embryonic development, cells may have to be re-programmed up to two or three times. Only cells programmed by the immune system will not be reprogrammed, which is, of course, a brilliant solution. The most important epigenetic markers affecting cell differentiation are DNA methylation and epigenetic markings of histone, i.e. DNA packaging proteins (including methylation, acetylation, ubiquitination, phosphorylation etc.).

These epigenetic information layers determining cell differentiation are set in epigenetic reprogramming by non-coding RNA molecules. The information transmitted by the MicroRNAs and lncRNAs will be stored in histone epigenetic markers that act as a biological database and an address system. Thus, all information related to the cell function is stored outside of the DNA sequences. In practice, this means activating or suppressing genes and transcriptional regions and bending chromatin to contact certain regions of DNA. As the organism adapts, it experiences the changes in epigenetic information structures. This often results in deleterious DNA sequence changes because methylation acts as a DNA stabilizer. When the methylation profiles change, the cell is exposed to oxidative stress that causes deamination of DNA bases, whereby the base may change. This is where a genetic mutation occurs. This is the most significant mechanism of DNA degradation.


When the organism adapts to, for example, a new nutritional type or a cooler climate, it is primarily necessary to investigate the changes in epigenetic profiles. DNA sequence changes may also occur, but they are also results of changed epigenetic profiles. Random mutations and natural selection have no role in the ecological adaptation of organisms. If we want to compare the genomic similarity between the two organisms, it should be done between the mechanisms affecting the cell differentiation. Thus, if we compare the human and chimpanzee lncRNA molecules, which set up the biological address database in the embryonic development, are the fallacies of the evolutionary theory revealed: The similarity of human and chimpanzee lncRNA molecules is only 29.8% !! So we're not related to apes. The evolutionary theory is the most serious heresy of our time. Don't get lost, good people.


Rapid ecological adaptation points to Design and Creation

Rapid ecological adaptation points to Design and Creation

If the emergence of a new species of birds does not take more than a couple of generations, there is evidence for Design and Biblical creation, the flood and the subsequent rapid formation of biodiversity.


Excerpt: "Researchers previously assumed that the formation of a new species takes a very long time, but in the Big Bird lineage it happened in just two generations, according to observations made by the Grants in the field in combination with the genetic studies."

We can observe everywhere the rapid ecological adaptation of organisms, based primarily on epigenetic gene regulation caused by diet type, climate and various stressors, which also causes genetic changes. However, most DNA sequence modifications result in genetic errors that lead to DNA degradation. The change is therefore not about mutations and natural selection, but due to mechanism-based ecological adaptation. Those mechanisms also cause changes to the pheromone production of the organism, which in turn controls its mating behavior. This is why scientists use the term 'species', although rather it should be said about breeds, for example.

There's no mechanism for evolution because any change in organisms is caused by epigenetic regulation of existing biological information OR loss of it. Don't be deceived.


The body's stress management is an irreducibly complex entity that has not been able to evolve

The body's stress management is an irreducibly complex entity that has not been able to evolve 

Our bodies constantly face different stress factors that can roughly be divided into physical and psychological stresses. Even walking from your warm home to a cold and damp, windy weather will cause a stress reaction in your skin because the skin's heat regulation proteins tend to balance heat fluctuations. If the mechanism does not work properly, you will not tolerate cold or hot.

To cope with stress situations, your body needs cortisol (hydrocortisone) produced by the cortex of the adrenal glands. The yield of cortisol is controlled by the mediator hormone ACTH, which in turn is produced by the pituitary gland. Hormone production of pituitary gland is in turn controlled by the CRH hormone produced by the hypothalamus and certain body cells. They also have an important link with our immune system. Also, intestinal bacteria have been found to have a clear connection with the production of CRH hormone.

Generally, producing cortisol is a highly regulated and controlled process because the body needs to get correct amounts of cortisol in the right time (over 140 tasks in a human body). Once the necessary control instructions have been given and cortisol released from the adrenal glands, a negative feedback loop guides the mechanism to suppress cortisol production at the time when the body responds to the stressor.

The following picture illustrates the mechanisms for stress management and the immune defense system and the connections between them. The system is irreducibly complex; even a disorder or problem in just one part of the system will collapse the whole system and the organism will die quickly. It is impossible for such a carefully regulated system, based on a number of elements, to evolve itself because the system works only as a complete entity.

Evolution theory is the most serious heresy of our time. Don't get lost.


Histone Code - A Biological Database

Readers, writers and erasers - Epigenetic markers of histones - a sophisticated biological database

The cell has a biological database that has sometimes been compared to the barcode system. These are epigenetic markers of histones, known to many different types. The most common are methylation, acetylation and ubiquitination. Histones are DNA packaging proteins around which DNA is interwoven. The cell uses the structure of chromatin to regulate and control the genes. The more open chromatin is, the more actively the gene is read in transcription. And vice versa, what is the more concealed in the structure of the histones, the more the cell holds the gene suppressed so it can not end up in transcription. The structure of the chromatin acts as an analogue regulator. Thus, epigenetic regulation works much more dynamically than an ON / OFF switch. Histone epigenetic markers have a very large regulatory effect, e.g. for alternative splicing of pre-mRNA. This mechanism makes it possible to use genetic material in a multi purpose way. For example, from human DNA 19,600 protein encoding genes, the cells can produce up to more than a million different proteins for different purposes of our body.

Histone epigenetic markers serve as a biological address database, keeping information on how the cell is to read genes. Histone markers are inherited by assistance of non coding RNA molecules. For example, lncRNA molecules have a great importance in this task. All the individual's characteristics are stored in the epigenetic markers of histones. They have a decisive influence on cell identity, that is, its differentiation process, so imbalances and disturbances in the histone markers database might cause serious diseases such as cancer.

Histone epigenetic markers have writers, readers, and erasers. These enzymes and proteins, in turn, are under the control of non coding RNA molecules. They are often transmitted by extracellular vesicles, which function, as carriers and mediators of miRNA molecules in cellular communication. This mechanism allows the cell to learn about the surrounding world, climate, nutrition, stress, etc. The erasers make it possible for the organism to adapt to the surrounding nature dynamically and also in reverse. Any change in organisms is based on epigenetic control of existing biological information or loss of information, whereby the cell activates alternative configurations to maintain the most important mechanisms for survival. Random mutations or natural selection have nothing to do with these designed mechanisms.

If the epigenetic regulatory layers experience disruption or imbalances, the DNA is exposed to harmful sequence errors, i.e. mutations. These include, for example, in the human genome already at the population level, tens of millions and have led to 208368 genetic mutations in human DNA. The annual growth was about 20,000. There is no mechanism for evolution because the genes of DNA do not control anything. The cell reads, regulates and uses them according to the adaptation needs. In adaptation, information typically disappears because variable methylation profiles trigger sequence errors and thus generate a defective gene material that the cell can not use. The biological address database, the histone code, is proof of design and creation. An unguided, random-based lottery system is not able to build such a high-tech information system. That is why every believer in evolution is deceiving himself. Don't get lost.


Dual-layer epigenetic gene regulation - Biological metadata points to Intelligent Design

Information layers around information layers work like a data container


Excerpt: "How can defective gene activity leading to cancer be avoided? Researchers at the University of Zurich have now identified a mechanism by which cells pass on the regulation of genetic information through epigenetic modifications. These insights open the door to new approaches for future cancer treatments.

...Methylation marks on DNA act as molecular switches that regulate gene activity in order to coordinate the cell's specialization within the organism. How this DNA methylation is faithfully regulated, and how it can become defective, has not yet been fully resolved. However, the consequences are well known: In many cancer types, the methylation is deposited in the wrong place. This leads to genes being read incorrectly.

Dual-layer epigenetic gene regulation

Scientists at the University of Zurich have now found new processes that regulate DNA methylation. Tuncay Baubec, professor at the Department of Molecular Mechanisms of Disease at the University of Zurich, and his team have shown that one particular protein plays an important part in this process: The DNA methyltransferase 3A (DNMT3A) enzyme is responsible for positioning the methylation to the right place on the DNA. "DNMT3A places itself preferably in close vicinity to genes that play an important role for development and makes sure that the DNA methylation around these genes is maintained," explains Massimiliano Manzo, lead author of the study. "The DNA methylation around these genes works like a container that ensures that H3K27me3, another epigenetic modification, which normally regulates these genes, is positioned correctly." This means that these essential genes are regulated by two epigenetic layers.
Increasing understanding of how cancer develops

The study's findings provide important basic insights for cancer research. DNMT3A is among the most frequently mutated genes in an aggressive type of leukemia, and it plays a significant role in how this disease develops. "Our findings point toward a previously unknown function of the DNMT3A protein in the interaction of these two epigenetic modifications that are normally not directly linked. We hope that these new insights will allow us to increase our understanding of the molecular mechanisms that result in cancer and to more effectively treat this aggressive type of leukemia," explains Professor Baubec."

My comment: Using containers in maintaining the integrity of biological information requires perfect software design. The DNA seems to be controlled by incredible mechanisms that refute Darwinian claims about random mutations and selection. Cellular data containers are comparable with human designed software and programming solutions. Cellular metadata points to Intelligent Design and Creation. Don't get lost.


Scientists need a human reference genome - Accurate DNA repair now possible

Lifestyle induced inheritable DNA mutations can be repaired on the atomic level

Excerpt: "Scientists at Harvard University and the Broad Institute of MIT and Harvard have developed a new class of genome editing tool. This new “base editor” can directly repair the type of single-letter changes in the human genome that account for approximately half of human disease-associated point mutations. These mutations are associated with disorders ranging from genetic blindness to sickle-cell anemia to metabolic disorders to cystic fibrosis.

The research team, led by David Liu, professor of chemistry and chemical biology at Harvard University, core institute member at the Broad Institute, and a Howard Hughes Medical Institute (HHMI) investigator, developed a molecular machine that can converts the DNA base pair A•T to G•C, without cutting the double helix, with high efficiency and virtually no undesired products. The development is an important addition to the growing suite of genome editing tools.

The new system is described in a paper published today in Nature. In addition to Liu, the study was led by Nicole Gaudelli, a postdoctoral fellow in Liu’s lab; Alexis Komor, a former postdoctoral fellow in Liu’s lab who is now an assistant professor at UCSD; graduate student Holly Rees; former graduate students Michael Packer and Ahmed Badran, and former postdoctoral fellow David Bryson.

The new system, dubbed Adenine Base Editor, or ABE, can be programmed to target a specific base pair in a genome using a guide RNA and a modified form of CRISPR-Cas9. It works by rearranging the atoms in a target adenine (A) — one of the four bases that make up DNA — to instead resemble guanine (G), and then tricking cells into fixing the other DNA strand to complete the base pair conversion, making the change permanent. As a result, what used to be an A•T base pair becomes a G•C base pair.

Not only is the system very efficient compared with other genome editing techniques for correcting point mutations, but there are virtually no detectable byproducts such as random insertions, deletions, translocations, or other base-to-base conversions.
Making this specific change is important because approximately half of the 32,000 disease-associated point mutations already identified by researchers are a change from G•C to A•T.

“We developed a new base editor — a molecular machine — that in a programmable, irreversible, efficient, and clean manner can correct these mutations in the genome of living cells,” said Liu, who is also the Richard Merkin Professor and Director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad. “When targeted to certain sites in human genomic DNA, this conversion reverses the mutation that is associated with a particular disease.”
ABE joins other base-editing systems pioneered in Liu’s lab, such as BE3 and its improved variant, BE4. Using these base editors, researchers can now correct all the so-called “transition” mutations — C to T, T to C, A to G, or G to A — that together account for almost two-thirds of all disease-causing point mutations, including many that cause serious illnesses for which there are no current treatments. Additional research is needed, Liu notes, to enable ABE to target as much of the genome as possible, as Liu and his students previously achieved through engineering variants of BE3."

My comment: The most common form of point mutations in the human DNA is CG > TA due to proclivity of methylated cytosine turning to thymine in circumstances where the DNA is exposed to oxidative stress, viral attacks or other disruptive contributors. Point mutations result in faulty gene sequences that are always critical and often harmful. They are the most common reason for disease-causing genetic mutations (total number 208,368 in October 2017. Annual growth was ~20,000) in the human DNA.

Because mutations are not resulting in evolution, but genetic degradation only, scientists need this kind of new technologies for being able to repair the human DNA and to restrain devolution from happening. However, scientists need a proper human reference genome. Will people then realize that the DNA genes are not determining human traits like height, intelligence, skin color etc.? And will they also realize that the theory of Evolution is a major lie?


60,000 generations of bacteria - But evolution has not been observed

Lenski's long term experiments with bacteria contradict with evolutionary expectations


Excerpt: "You may have heard of the famous Lenski experiment. Dr. Richard E. Lenski is an evolutionary biologist who began a long-term experiment on February 24, 1988 that continues today. It looks for genetic changes in 12 initially identical populations of Escherichia coli bacteria that have been adapting to conditions in their flasks for over 60,000 generations. I have simplified a report by Scott Whynot, who studied 26 peer-reviewed scientific articles authored by Dr. Lenski (with others) published between 1991 and 2012. These papers represent the major genetic findings from 21 years of the experiment.

1. There was an insertion mutation that inhibited transcription of DNA involved in cell wall synthesis.

2. There was an insertion mutation in a regulatory region that encodes two proteins involved with cell wall synthesis. This may have led to larger cells.

3. A mutation in a gene led to a defect in DNA repair.

4. An insertion mutation may have knocked out a gene involved in programmed cell death and response to stress.

5. There was another mutation in a gene involved in response to stress, disrupting its function.

6. There was a mutation in the gene that encodes an enzyme that loosens DNA coils, leading to an increase in DNA supercoiling.

7. There was an insertion mutation in a gene that represses the production of nicotinamide adenine dinucleotide (NAD), a molecule that participates in many metabolic reactions, some affecting longevity. This might allow more NAD production.

8. The researchers noted an insertion mutation that they think inactivated a gene, resulting in greater glucose uptake. Glucose is a limited energy source in the experiment.

9. Deletion mutations caused the loss of the ability to catabolize D-ribose, an energy source that is not available in the experiment.

10. There was a mutation in a gene regulating transport of the sugar maltose, an energy source that is not present in the experiment.

11. After about 30,000 generations, the E. coli in one of the twelve isolated populations began to utilize an energy source, citrate, that they normally could not use in the presence of oxygen. E. coli already have the ability to transport and metabolize citrate where there is no oxygen, but they do not produce an appropriate transport protein for an environment with oxygen. In E. coli DNA, the gene for the citrate transporter that works without oxygen is directly upstream from genes for proteins with promoters that are active in the presence of oxygen. A replication of the region happened to put the transporter gene next to one of these promoters, so it could now be expressed in the presence of oxygen.
Except for number 11, the changes found in over 60,000 generations of bacteria were due to the disruption, degradation, or loss of genetic information. The ability to use citrate in the presence of oxygen, trumpeted by evolutionists as a big deal, was the result of previously existing information being rearranged, not the origin of new information. Mutations that result in a gain of novel information have not been observed."

My comment: 60,000 generations of bacteria show us the true nature of how adaptation of organisms occur and what it result in. Alterations in epigenetic layers lead to harmful sequence errors at the DNA level. Switching between different traits has its cost; an inevitable genetic degradation. This same phenomenon is a scientific fact within all kind of organisms in nature. Mutations are not random changes. Organisms have several mechanisms by which they are able to make use of genes. Non coding RNA molecules monitor the circumstances of surrounding environment and they transmit the information to the cell that is able to use the DNA as a library for producing necessary proteins needed in survival. The theory of evolution is a major lie, because:
- Increase of information leading to growth of structural or functional complexity has never been observed.
- Switching between diferent traits has a heavy cost: GENE LOSS.
- All changes in bacteria were due to existing biological information or rearrangement of it. Alterations occurred due to nutrition dependent reasons.
- Bacteria stay bacteria after 60,000 generations. 
- The obvious loss of genetic material has happened very fast.


Worms learn to smell danger - more than a reaction

Olfactory experience primes the heat shock transcription factor HSF-1 to enhance the expression of molecular chaperones in C. elegans


Excerpt: "Worms can learn. And the ways they learn and respond to danger could lead scientists to new treatments for people with neurodegenerative diseases.

University of Iowa researchers researchers studied how roundworms—some of the most abundant animals on Earth—react to stressful situations by exposing them to the scent of a lethal bacterium. One group of roundworms exposed to the smell primed a defense mechanism that, when activated by stress, protected the worms' cells and increased the cells' survival. The group that wasn't exposed to the odor didn't prime its defense systems. When both groups were put in physical contact with the deadly bacterium, the roundworms that were exposed to the smell activated their cellular defenses more quickly, and more survived.

The finding could usher in a new, non-pharmaceutical approach to treating neurodegenerative diseases such as Alzheimer's and Huntington's. These diseases occur when nerve cells in the brain or peripheral nervous system become damaged, lose function over time and ultimately die. Although treatments may help relieve some of the physical or mental symptoms associated with neurodegenerative diseases, there is no cure or way to slow the progression of these diseases.

The research also could help with disorders associated with aging, such as dementia, which involve the accumulation of protein damage in cells that the human central nervous system does not address, for reasons largely unknown.
"Theoretically, it should be possible to treat these types of diseases if we can figure out how to stimulate that defense mechanism in people and have it activated more consistently to fix damaged cells," says Veena Prahlad, assistant professor of biology at the UI and corresponding author on the paper, published Oct. 17 in Science Signaling. "We'd need to find the same sensory triggers in humans as we have demonstrated...in worms."

The researchers zeroed in on a defense mechanism common to all plants and animals known as the heat shock response.

This mechanism—activated by changes in temperature, salinity, and other stressors—triggers the production of a class of proteins called molecular chaperones, which seek out and repair or get rid of damaged proteins that have become toxic to the cell. The goal is to prevent an overload of damaged proteins in the cell, which would kill it.

In humans, as in the roundworms studied by Prahlad, a key protein involved in synthesizing molecular chaperones is called the heat shock transcription factor, or HSF1. Researchers know that HSF1 plays a role in guarding against protein damage in neurons that can lead to neurodegenerative diseases. But they thought it was activated only as a response to an overload of damaged proteins in cells. But Prahlad, who has studied HSF1 since she was a postdoctoral researcher, hypothesized it may be more than a reactive element. Maybe, she thought, HSF1 could be put on standby, and thus, could be activated more quickly when a threat occurs.

A big test of her idea came when she and UI graduate student and first author Felicia Ooi exposed one group of worms to the odor of the deadly bacterium PA14 while another group was given the odor of a different, benign bacterium. The group exposed to the PA14 odor activated twice the number of molecular chaperones than the group given the benign odor. Moreover, the worms exposed to the PA14 odor had a 17 percent higher survival rate after 18 hours than the worms given the odor of the benign bacterium.

Prahlad says she thinks the worms exposed to the PA14 odor "learned" the smell—and the threat that it presents—and stored that memory.

"We show in this paper that (the HSF1 response) is not a reaction," says Prahlad, who also holds an appointment in the UI's Aging Mind and Brain Initiative. "The animal turns it on in anticipation, and it does that by learning about the threat in its environment." "

My comment: Here we have a wonderful example of mechanism that refutes darwinian fairytales of mutations and selection. The fact that these smallest multicellular organisms are able to learn in such a sophisticated way points to incredible design and creation. Roundworms are able to set their defense mechanism at standby mode so that they can rapidly switch it on after sensing the danger with their olfactory receptors. Enhancing the expression of molecular chaperones, proteins that assist produced proteins to fold or unfold correctly, is an epigenetic mechanism. It's affected by miRNA regulation, DNA methylation and histone epigenetics. The link between olfactory receptors, gene expression and learning is a very interesting topic. It tells us about designed mechanisms that help and prepare organisms to survive. These mechanisms have nothing to do with random mutations and selection. The theory of evolution is a hollow fairytale. Don't get lost.


These fine-tuned protein complexes don't tolerate mutations

Cohesin and Mediator protein complexes regulate cell type specific DNA loop structures to control gene expression


Excerpt: "Each cell type, such as skin cells, nerve cells, or embryonic stem cells, has its own gene expression program to maintain its cell state. For gene activation, transcription factors and gene expression machinery (RNA polymerase), bound to two different parts of the DNA called the promoter and the enhancer, must come in contact. This contact, which is facilitated and maintained by protein complexes called Mediator and Cohesin, forms a set of DNA loops that is specific to each cell type.

Problems with this DNA loop structure can interfere with the activation of cell-type-specific genes, which can cause the cell to lose its normal state. Indeed, mutations in Mediator and Cohesin, the protein complexes that contribute to DNA loop formation, at cell-type-specific genes, can cause various developmental syndromes and diseases, including Opitz-Kaveggia syndrome, Lujan syndrome and Cornelia de Lange syndrome.

According to the Young lab’s paper, published online in Nature this week, a DNA loop formed at the beginning of cell-type-specific genes enables activation of these genes. Each cell type, such as skin cells, nerve cells, or embryonic stem cells, has its own gene expression program to maintain its cell state. For gene activation, regulatory factors and gene expression machinery, bound to two different parts of the DNA called the promoter and the enhancer, must come in contact. This contact, which is facilitated and maintained by protein complexes called Mediator and Cohesin, forms a set of DNA loops that is specific to each cell type.

“That’s such a surprise,” says Young, whose lab is deciphering the overall cellular circuitry required to regulate gene expression and cell state. “We thought that a loop of DNA probably formed at the beginning of some genes—it’s an old model—but we didn’t expect that loops are formed by these complexes at active cell-type-specific genes.”
Problems with this DNA loop structure can interfere with the activation of cell-type-specific genes, which can cause the cell to lose its normal state. Indeed, mutations in Mediator and Cohesin, the protein complexes that contribute to DNA loop formation, at cell-type-specific genes, can cause various developmental syndromes and diseases."


Excerpt: "But cohesin really only affects looping that brings genes on the same chromosome into contact. A second, still-undefined mechanism seems to bring genes from different chromosomes together, the team notes. The changing landscape of loops helps cells quickly change which genes are active."

My comment: The cell uses these protein complexes for bringing genes into contact so that gene expression is perfectly controlled. The 3D landscape is efficiently changed along the needs of adaptation or cellular differentiation program. There are several epigenetic factors affecting this 3D looping: The DNA methylation, histone markings and non coding RNA molecules. Mutations in these fine-tuned protein complexes are associated with various developmental syndromes and diseases.

These mechanisms show us again that the DNA is not controlling cellular processes. Instead, the cell uses DNA genes as it needs them for achieving its goals. These sophisticated mechanisms point to Intelligent Design and Creation.


Hopping molecule clusters control genes in Energy efficient way

Cells can respond as quickly as possible to signals from the outside


Research at the University of York has revealed that genes are controlled by 'nano footballs' -- structures that look like footballs but 10 million times smaller than the average ball.

Excerpt: "By placing tiny glowing probes on transcription factors -- special chemicals inside cells which control whether a gene is switched 'on' or 'off' -- researchers gained a remarkable new insight into the way in which genes are controlled.

Crucially, they discovered that transcription factors operate not as single molecules as was previously thought, but as a spherical football-like cluster of around seven to ten molecules of roughly 30 nanometres in diameter.

The discovery of these nano footballs will not only help researchers understand more about the basic ways in which genes operate, but may also provide important insights into human health problems associated with a range of different genetic disorders, including cancer.

The research, supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and published in eLife was carried out by scientists from the University of York, and the University of Gothenburg and Chalmers University of Technology, Sweden.

The researchers employed advanced super-resolution microscopy to look at the nano footballs in real time, using the same type of yeast cells utilised in baking and brewing beer.

Professor Mark Leake, Chair of Biological Physics at the University of York who led the work, said: "Our ability to see inside living cells, one molecule at a time, is simply breathtaking.

"We had no idea that we would discover that transcription factors operated in this clustered way. The textbooks all suggested that single molecules were used to switch genes on and off, not these crazy nano footballs that we observed.

The team believe the clustering process is due to an ingenious strategy of the cell to allow transcription factors to reach their target genes as quickly as possible.

Professor Leake said: "We found out that the size of these nano footballs is a remarkably close match to the gaps between DNA when it is scrunched up inside a cell. As the DNA inside a nucleus is really squeezed in, you get little gaps between separate strands of DNA which are like the mesh in a fishing net. The size of this mesh is really close to the size of the nano footballs we see.

"This means that nano footballs can roll along segments of DNA but then hop to another nearby segment. This allows the nano football to find the specific gene it controls much more quickly than if no nano hopping was possible. In other words, cells can respond as quickly as possible to signals from the outside, which is an enormous advantage in the fight for survival."

Genes are made from DNA, the so-called molecule of life. Since the discovery that DNA has a double helix shape, made in the 1950s by pioneering biophysics researchers, much has been learned about transcription factors which can control whether a gene is switched on or off.

If a gene is switched on, specialised molecular machinery in the cell reads off its genetic code and converts it into a single protein molecule.Thousands of different types of protein molecules can then be made, and when they interact that can drive the building of all of the remarkable structures found inside living cells.

The process of controlling which genes are switched on or off at any particular point in time is fundamental to all life. When it goes wrong, this can lead to serious health problems. In particular, dysfunctional switching of genes can result in cells which grow and divide uncontrollably, which can ultimately lead to cancer.

This new research may help provide insights into human health problems associated with a range of different genetic disorders. The next stages will be to extend this research into more complicated types of cells than yeast -- and ultimately into human cells."

My comment: Genes are controlled by several epigenetic factors, like these nano molecule clusters. The cell is able to produce even thousands of different proteins by using only one sequence of the DNA by a very clever mechanism called alternative splicing. These nano footballs point to Intelligent Design. The cell can re-use them on several locations along the needs of adaptation. Here we have again a mechanism that refutes hollow claims of random mutations and selection. All change in organisms is based on epigenetic regulation of existing biological information or loss of it. That's why there's no mechanism for evolution. Don't get misled.


Epigenetic alterations result in harmful mutations

Modifications in methylation patterns lead to harmful genetic mutations


Excerpts: "Diverse epigenetic modification patterns can affect the types and frequencies of genetic alterations at the neighboring chromatin regions. Integrative analysis of whole genome sequencing with epigenome sequencing have identified how the epigenetic landscape influences the accumulation of genetic alterations during hepatocarcinogenesis. The analysis also showed that several cancer driver genes are mutated either by genetic or epigenetic alterations. Genetic mutations that are affected or substituted by epigenetic alterations include single nucleotide variant (SNVs) mutations, small insertions and deletions (indels) and DNA copy number variations (CNVs). We have summarized recent findings that demonstrate molecular links between genetic mutations and epigenetic modifications.
Because diverse mutational mechanisms are at play during tumorigenesis, the SNV patterns of each tumor are different and reflect the nature of the tumor-inducing conditions. HCC shows high frequencies of C to T, C to A and T to C nucleotide substitutions. Among these, C to T transitions at CpG dinucleotide sequences are caused by the relatively elevated rate of spontaneous deamination of 5-methyl-cytosine in tumors. Thus, the DNA demethylation levels of tumor cells could influence the mutation frequencies induced by the deamination process. In addition, the significant upregulation of the APOBEC family in HBV- and HCV-HCC promotes C to T and C to A mutations by deaminating cytidine to uracil (C to U), coupled with the base excision repair and DNA replication processes. Besides APOBEC enzymes, several cellular and viral proteins also affect base substitutions epigenetically. A methyl-CpG-binding protein, MBD4, can affect the C to T transition rate, probably by regulating accessibility of the methylated C for deamination or repair enzymes.

DNA methylation status also has a strong effect on chromosomal integrity. Global DNA hypomethylation is observed in HCC and can induce activation of transposons and chromosomal instability, thus contributing to the generation of a large number of CNVs during hepatocarcinogenesis. Hypomethylation-associated reactivation of repetitive elements such as LINE-1, ALU and juxtacentromeric SAT2 is frequently observed in HCC along with copy number variations caused by insertions and deletions. Intriguingly, the loss of repetitive DNA appears tightly associated with its hypomethylation.

Acetaldehyde and free radicals generated by metabolizing alcohol induce DNA damage and oxidative stress, which often accelerate monocyte activation and telomere shortening. The alcohol-derived risk factors (acetaldehyde and free radicals) seem to function mainly as a mutagen affecting DNA integrity; however, its role in epigenetic regulation in liver cells is now being discovered."

My comment: We've been taught that epigenetic modifications don't contribute to the DNA but as we can see, this is not the case. It's obvious that changing methylation patterns (also called as methylation profiles) result in changes in DNA sequences. The most typical factors impacting on methylation patterns by abnormal way are oxidative stress, viruses, alcohol, smoking and environmental toxins. Shifting diet types also cause alterations in epigenetic patterns possibly leading to harmful genetic mutations. Life habits are the most significant reason for rapidly increasing repertoire of disease-causing genetic mutations in the human DNA. There are already 208,368 of them at population level. The annual increase was about 20,000. But modern scientists are not aware of beneficial random mutations. That's why there are no mechanisms for evolution. All change in organisms is based on epigenetic regulation of existing biological information OR loss of it. Don't get misled. 


This is why scientists should focus on Epigenetics

This is why Mendelian laws are not valid anymore

1. "A few years later, the situation became even worse with the discovery of alternative splicing. In alternative splicing, a given ‘split gene’ can code for various different proteins, depending on whether this or that exon is expressed at a given time (for instance a certain exon is expressed in embryos, another one is expressed in the adult organism)."

The most significant EPIGENETIC factors modulating the alternative splicing machinery:
a. microRNAs  b. DNA methylation  c. Histone markers

2. "Other phenomena are also quite challenging for the notion of a gene as ‘no more than a coding sequence’: assembled genes (where germinal sequences, often designated as ‘genes’, are assembled to make a single somatic gene, a situation commonly found in immunogenetics: all antibodies are coded by assembled genes); inversion of the reading frame (meaning that the same DNA sequence can be transcribed in both directions, resulting in different proteins)."

Especially microRNAs (EPIGENETICS) mediate the production of antibodies.

3. "Partial overlapping of the reading frames (the same sequence translated in different frames can give up to two or even three different proteins)."

Transcription of overlapping reading frames is regulated by EPIGENETIC mechanisms:
a. DNA methylation  b. microRNAs  c. Histone markers

4. "Multiple initiation and termination sites of transcription (producing a multiplicity of RNA molecules out of which proteins will eventually be synthesized)."

This is based on EPIGENETIC mechanisms.

5. "Non-universality of the genetic code (e.g., a slightly different code for nuclear genes and cytoplasmic genes: this means that the same sequence, in the same organism, can lead to different proteins)."

Because protein production is mediated by several EPIGENETIC mechanisms.

6. "This is only a partial list. Today, many molecular processes are known that challenge the traditional ‘one gene-one protein’ dogma. In reality, it seems hopeless to provide a general definition of the gene on the basis of exclusively molecular criteria."

7. "The discovery of non-coding RNA has maybe been the most impressive discovery in molecular biology since 2000. Recent data show that 98.5% of our genome is not translated into proteins, but more than 70% is transcribed into RNA (EPIGENETICS). Furthermore, 70,000 promoter regions (EPIGENETICS) (the sites where proteins bind to control gene expression) and 400,000 enhancers (EPIGENETICS) (regulatory sites that affect the expression of distant genes) have been discovered in the human genome. These findings suggest that the information contained in our genome goes far beyond the usual picture of 20,000–25,000 protein-coding genes. (My comment: 19,600) There are many more functional units than those protein-coding genes. Given this situation, one might think that the word ‘gene’ could be abandoned, and replaced by more precise terms."

My comment: The DNA sequences, often designated as 'genes', are very raw material for several epigenetic mechanisms that control cellular processes. All change in organisms is based on epigenetic regulation of existing biological information OR loss of it. That's why there are no mechanisms for evolution. Life is not driven by DNA's gene sequences. Genes are driven by life(style).


Smoking causes changes in methylation profiles - First step in lung cancer development

Genetic mutations caused by epigenetic alterations


Excerpt: "Scientists at the Johns Hopkins Kimmel Cancer Center say they have preliminary evidence in laboratory-grown, human airway cells that a condensed form of cigarette smoke triggers so-called "epigenetic" changes in the cells consistent with the earliest steps toward lung cancer development.

Epigenetic processes are essentially switches that control a gene's potentially heritable levels of protein production but without involving changes to underlying structure of a gene's DNA. One example of such an epigenetic change is methylation—when cells add tiny methyl chemical groups to a beginning region of a gene's DNA sequence, often silencing the gene's activation. (My comment: Even an addition/removal of one methyl group might significantly influence the protein interactions and the identity of the cell.)

"Our study suggests that epigenetic changes to cells treated with cigarette smoke sensitize airway cells to genetic mutations known to cause lung cancers," says Stephen Baylin, M.D., the Virginia and D.K. Ludwig Professor for Cancer Research and professor of oncology at the Johns Hopkins Kimmel Cancer Center. Details of the scientists' experiments are described in the Sept. 11 issue of Cancer Cell.

For two decades, scientists have known some of the genetic culprits that drive lung cancer growth, including mutations in a gene called KRAS, which are present in one-third of patients with smoking-related lung cancers, according to Baylin. Genetic and epigenetic changes also occur when normal cells undergo chronic stress, such as the repeated irritation and inflammation caused by decades of exposure to cigarette smoke and its contents.
Baylin and Johns Hopkins scientist Michelle Vaz, Ph.D., first author on the study, suspected that the interplay of epigenetic and genetic changes may occur when normal lung cells develop into cancer, but, Baylin says, the timing of such changes was unknown.

To create the effect of tobacco smoke on cells, Vaz, Baylin and their colleagues began their studies with human bronchial cells, which line the airways of the lungs, and grew them in a laboratory. Every day for 15 months, the scientists bathed the cells with a liquid form of cigarette smoke, which they say is comparable to smoking one to two packs of cigarettes daily.

The scientists recorded the molecular and genetic changes in the smoke-exposed cells over 10 to 15 months, which the scientists say may be similar to 20 to 30 years of smoking, and compared the changes to bronchial cells that had not been exposed to the liquid smoke.

After 10 days of smoke exposure, the scientists found an overall increase in DNA damage responses to so-called reactive oxygen species within the cells. Reactive oxygen species, also called free radicals, are chemicals that typically contain oxygen, are known to be found in cigarette smoke, and cause DNA damage in cells.

Between 10 days and three months, the cells exposed to smoke had a two- to four-fold increase in the amount of an enzyme called EZH2, which works to dampen the expression of genes. Baylin and other scientists have shown that EZH2 and its effects can precede abnormal DNA methylation in gene start sites.

After EZH2 enzymes rise, their levels taper off, and then, the scientists found two to three-fold increases in a protein called DNMT1, which maintains DNA methylation in the "start" location of a variety of tumor suppressor genes that normally suppress cell growth. When these genes are silenced a barrier is removed that might otherwise stop the cells from growing uncontrollably—a hallmark of cancer.

A host of other genes (My comment: mediated by non coding RNA molecules), which control many other cellular processes do not show such abnormal DNA methylation after smoke exposure.

Baylin says certain genes that control cell growth 
(My comment: mediated by non coding RNA molecules) get turned down periodically during certain stages of life, including embryogenesis, when organisms are growing and developing rapidly. These genes can normally be turned on when cells need to stop growth and allow cells to mature. Chronic cigarette smoke exposure, as noted in many human cancers, tends to block these cell maturation genes from properly turning on, says Baylin.

At the end of six months, the amount of EZH2 and DNMT1 enzymes had tapered off in the cells exposed to the smoke. However, the impact of the two methylation-regulating enzymes was still seen at 10 to 15 months, when scientists found decreased expression of hundreds of genes—many of which are key tumor suppressor genes such as BMP3, SFRP2 and GATA4—in the smoke-exposed cells and a five- or-more-fold increase in the signaling of the KRAS oncogene that is known to be mutated in smoking-related lung cancers.

However, no mutations were found in the KRAS gene itself or the tumor suppressor genes during the 15-month period of cigarette smoke exposure. These abnormally methylated and silenced genes, says Baylin, would have blocked the increase in KRAS signaling if the genes had been properly activated under smoke-free circumstances.

The scientists also found that the timing of epigenetic and genetic events may be key to lung cancer development. They tested this by inserting mutations into the KRAS gene in the DNA of cells exposed to the cigarette smoke condensate for six months as well as those exposed for 15 months. The scientists found that the inserted mutation transformed cells into cancer in only the 15-month cells, where methylation was fully established, but not in the six-month-exposed cells.

Vaz and Baylin say the results suggest that early epigenetic changes triggered by chronic cigarette smoke exposure can build up over time and make the airway cells increasingly sensitive to responding to mutations that initiate cancer.

They say that smokers can best lower their risk of cancer by quitting altogether, and the sooner a smoker quits, the lower their lung cancer risk may be. Their analysis of data in previous studies done by The Cancer Genome Atlas group have shown that the types of abnormal methylation levels they found are lower in smokers who have quit for more than 10 years than those who have not quit.

It may be possible to use de-methylating drugs, they say, for people with higher than normal risk for lung cancer, such as people who have had surgery for early forms of the disease. Such drugs are currently used in clinical trials for certain types of cancer and are standard therapy for a type of pre-leukemia condition.

The scientists caution that their model, as is the case with any laboratory model, may not be exactly what occurs in people during a lengthy period of smoking, but they say it's a first step in understanding the epigenetic processes that may occur early in the transformation of cells into lung cancer."

My comment: This is a typical example of genetic alterations driven by life habits. Cells are exposed to free radicals and oxidation by several other factors that result in aberrant methylation patterns that sensitize cells to genetic mutations. A minority of these genetic errors are ended up to germ line cells. This is one significant reason for human genetic degradation. It is an inevitable phenomenon but people are catalyzing it with poor nutrition, smoking, alcohol consumption and other bad life habits.

Organisms in nature are also experiencing alterations in methylation patterns. This same phenomenon exposes cells to genetic errors that weaken the gene pool. All changes in organisms are based on epigenetic regulation of existing biological information OR loss of information. That's why there are no mechanisms for evolution. Don't get lost.


Supercomputer models one second of human brain activity

It took 40 minutes for a supercomputer with 705,024 processor cores and 1.4 million GB of RAM to simulate ONE second of human brain activity

Excerpt: "The most accurate simulation of the human brain to date has been carried out in a Japanese supercomputer, with a single second’s worth of activity from just one per cent of the complex organ taking one of the world’s most powerful supercomputers 40 minutes to calculate.

Researchers used the K computer in Japan, currently the fourth most powerful in the world, to simulate human brain activity. The computer has 705,024 processor cores and 1.4 million GB of RAM, but still took 40 minutes to crunch the data for just one second of brain activity.

The project, a joint enterprise between Japanese research group RIKEN, the Okinawa Institute of Science and Technology Graduate University and Forschungszentrum J├╝lich, an interdisciplinary research center based in Germany, was the largest neuronal network simulation to date.
It used the open-source Neural Simulation Technology (NEST) tool to replicate a network consisting of 1.73 billion nerve cells connected by 10.4 trillion synapses.

While significant in size, the simulated network represented just one per cent of the neuronal network in the human brain. Rather than providing new insight into the organ the project’s main goal was to test the limits of simulation technology and the capabilities of the K computer."

My comment: The astonishing complexity and efficiency of the human brain point to Intelligent Design and Creation. Even one cell is hyper complex: In a single human cell, more than 100,000 different biochemical reactions happen every second. Just take a look at the incredible complexity of metabolic pathways of a human cell to have an idea of how perfectly designed the cellular mechanisms are.