söndag 18 november 2012

Nature, nurture and natural selection. Epigenetic memory.

Nowhere has the debate about nature and nurture been so controversial as in the study of mental ability in humans. IQ is a phenotypic measurement of relative performance on a series of mental ability tests. Our immune system is a sort of loose brain, in that most immune cells float free in our body, while our brain's neurons function within a highly interconnected web. Both systems are functionally similar.

As Jean Piaget used to say, intelligence is what you use when you don’t know what to do, when all the standard answers are inadequate.  To be smart is another thing. It is about making the right choises. We can subconsciously try out variations, using many brain regions. Eventually, as quality improves, we become conscious of our new invention. 

This is when we become aware of our intentions and thoughts? As examle mathematics? The Libet readiness potential?


Brain developement and nature - nurture effect.
Heritability patterns of IQ for young, preschool individuals are generally more to the nurture factors than for elder humans. How is this tested when we know that the developement of the nerves and theit net formations in the brain is very much depending on the nurture effects? Twins have been used in the majority of studies to estimate the heritability of IQ, both monozygote and dizygote twins.  MZ twins are substantially more similar in IQ than DZ twins, whether they are raised together or apart. Reported estimates of heritability for IQ from twin studies are remarkably consistent in the range of 0.5–0.8, across many age groups. Studies with adults show that they have a higher heritability of IQ than children do and that heritability could be as high as 0.8. Here can you also test your IQ.

Gerald Edelman won the Nobel Prize in 1972 for his discovery that the immune system doesn't operate through an instruction/memory model, as had been thought, but rather through evolutionary natural selection procedures. He found, rather, that through natural selection processes occurring over eons of time, we are born with a vast number of specific antibodies that each recognize and respond to a specific type of harmful invader that shares our environment. If we lack such a natural immunity to a specific invader (such as the AIDS virus), we may die if infected. Our immune system can't learn how to destroy the invader; it simply has or hasn't the capacity at birth. Edelman then studied our functionally similar brain to see whether it also operates principally on natural selection, rather than on instruction and learning. His controversial theory, Neural Darwinism, (here a review) argues that our brain does operate on the basis of natural selection—or at least that natural selection is the process that explains instruction and learning. Neuronal selection is another term with good results.

The powerful role that emotion plays in regulating brain activity, and the preponderance of parallel (rather than linear) processing in our brain, points to a biological model, not technological.

Edelmann proposes that the electrochemical dynamics of our brain's development and operation resemble the rich, layered ecology of a jungle environment. A jungle has no external developer, no predetermined goals. Indeed, it's a messy place characterized more by organic excess than by goal-directed economy and efficiency. No one organism or group runs the jungle. All plants and animals participate in the process, each carrying out a variety of ecological functions. The jungle environment doesn't instruct organisms how to behave, for example, by teaching trees how to position their limbs and roots to get sunlight and soil nutrients. Evolution works by selection, not instruction. The environment selects from among the built-in options available—it doesn't modify (instruct) the competing organisms. (No homunculus is there?) An infant brain doesn't have to learn how to recognize specific sounds and line segments; such basic neural networks are operational at birth. We don't teach a child to walk or talk; we simply provide opportunities for adaptations to an already operational process. Gazzaniga (1992) argues that all we do in life is discover what's already built into our brain. What we see as learning is actually a search through our brain's existing library of operating networks for the combinations of those that best allow us to respond to the immediate challenge; our DNA couldn't possibly encode our brain's networks for every possible combination of sights/sounds/smells/textures/tastes/movements that our brain can process. Instead, it encodes a basic developmental program that regulates how neurons will differentiate and interconnect.

The homunculus-theory has been a big obstacle in biology.He has unconscious thoughts, here discussed by Fracis Crich and Christof Koch, 2000.

Many has thought of the nurture side as being dominant, but these new theories argue that nature plays a  more important role than previously believed. They also suggest that many current beliefs about instruction, learning, and memory are wrong. The theories will become culturally controversial because they will require reconceptualizations of such concepts as parenting, teaching, learning, identity, free will, and human potential. Further, some people may misuse the theories to support racist, sexist, and elitist beliefs. Certainly those who reject Darwinian evolution will be disturbed by the evolutionary base of the new theories.

Fernando et al. suggests a neuronal basis for causal inference, function copying, and natural selection within the human brain. To date, no model of neuronal topology copying exists. We present three increasingly sophisticated mechanisms to demonstrate how topographic map formation coupled with Spike-Time Dependent Plasticity (STDP) can copy neuronal topology motifs.  A unit of selection is an entity that can replicate, and have hereditary variation. If these units have differential fitness they can evolve by natural selection.
Both Edelman and Changeux's groups have produced an impressive range of detailed models of hill-climbing type (exploration and exploitation) algorithms that can explain a wide range of behavioural and cognitive phenomena at various levels of abstraction [16]; such as category formation [12], reinforcement learning using spike-time dependent plasticity modulated by dopamine reward [17], visual-motor control in a robotic brain-based device [18], temporal sequence learning [19], effortful cognition in the Stroop task [20], and planning [21]. Importantly, both these research programs avoid the need for replication of neuronal groups, i.e. none of their algorithms require units of selection. The algorithms of Edelman and Changeux fundamentally consist of a population of stochastic hill-climbers [25]. Each neuronal group is randomly initialized, and those groups that are closest to a good solution obtain a greater quantity of synaptic resources allowing them to ‘grow’ and/or ‘change’. 

The heritability of IQ , (here wikipedia), investigates the relative importance of genetics and environment for phenotypic variation in intelligence quotient (IQ) in a population. If there is biological inheritance, heredity, of IQ, then the relatives of a person with a high IQ should exhibit a comparably high IQ with a much higher probability than the general population.

In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence.
This is why the differentiated cells in a multi-cellular organism express only the genes that are necessary for their own activity. Epigenetic changes are preserved when cells divide, but usually (?) not into the germline, which is conserved, sheltered, and divide very slowly (in off-state).

Several neurophysiological factors have been correlated with intelligence in humans, including the ratio of brain weight to body weight and the size, shape and activity level of different parts of the brain. Specific features that may affect IQ include the size and shape of the frontal lobes, the amount of blood and chemical activity in the frontal lobes, the total amount of gray matter in the brain, the overall thickness of the cortex and the glucose metabolic rate.

IQ is a polygenic trait (50 genes?) under normal circumstances according to recent research. However, certain single gene genetic disorders can severely affect intelligence, with phenylketonuria as an example. The example of phenylketonuria (PKU) is informative. Untreated, this is a completely penetrant genetic disorder causing brain damage and progressive mental retardation. PKU can be treated by the elimination of phenylalanine from the diet. Hence, a character (PKU) that used to have a virtually perfect heritability is not heritable any more if modern medicine is available (the actual allele causing PKU would still be inherited, but the phenotype PKU would not be expressed anymore).

Various studies have as instance found the heritability of IQ to be between 0.7 and 0.8 in adults and 0.45 in childhood in US.

Governments have implemented several health policies regarding nutrients and toxins known to influence cognitive function, as laws requiring fortification of certain food products and laws establishing safe levels of pollutants (e.g. lead, mercury, and organochlorides). Improvements in nutrition, and in public policy in general, have been implicated in worldwide IQ increases.

This new field of epigenetics means that a lot of the traditional assumptions in the field of genetic engineering are dangerously wrong. For example, the assumption that it is only the sequence of codons that create certain behaviours or attributes. It is not only the sequence but how that sequence interacts with other sequences which determines it's function - that means that a lot of the richness of expression is being completely stultified when they simply worry about the basic sequence, as they do in genetic modification.

Matt Ridley blog: In other words, hygienic, well-fed life enables people to maximize their genetic potential so that the only variation left is innate. Intelligence becomes significantly more heritable when environmental hurdles to a child's development have been dismantled. 
An objection to this is that in the well-fed conditions there are lots of diseases, so stress is obviously also a shelter for us. This is seen as instance in the cancer research on chaperones, or stress-proteins, also on kinases and regulation.

The American Psychological Association's report "Intelligence: Knowns and Unknowns" (1995) states that "there is no doubt that normal child development requires a certain minimum level of responsible care. Here, environment is playing a role in what is believed to be fully genetic (intelligence) but it was found that severely deprived, neglectful, or abusive environments have highly negative effects on many aspects of children's intellect development.  Regarding sex differences so have most standard tests of intelligence been constructed to show equal results, but some studies show small differences. Males do better on visual-spatial tasks, with a particularly large difference on mental rotation (nearly 1 SD), which is significant for their generally better performance in tasks that involve aiming and throwing. Males also do relatively better on on tests of proportional and mechanical reasoning as well as on mathematics. Females do better on verbal tests and some memory tests. They do relatively better in tests of literature, English composition, Spanish, reading, and spelling. More males have dyslexia and stuttering. Possible causes include gender roles and differences in brain structure which in turn may be due genetics and/or environment. Differences in sex hormones may be another explanation. Female exposure to high levels of male hormones in utero is associated with higher spatial abilities as well as more spatial ability as well as more play with "boys' toys" and less with 'girls' toys". Males with higher testosterone levels do better on visuo-spatial abilities and worse on verbal abilities. Older males given testosterone score better on visuo-spatial tests."

I almost never played with dolls nor 'girl toys'. More about gender differencies here.
  • HEREDITY refers to traits passing on from parent to offspring.
  • HERITABILITY refers to the proportion/percentage of VARIABILITY that can be attributed to genetic differences. Please note that this does not mean that that same proportion of the trait is attributed to Genetics. 
Note: Cognition, thinking, will, intention, consciousness are still open fundamental questions. Correlation studies are also just that, correlations. This maybe also shed some light also on the question what exactly is natural selection? Natural selection acts on the phenotypePhenotype is determined by an organism's genetic make-up (genotype) and the environment in which the organism lives.
A prerequisite for natural selection to result in adaptive evolution, novel traits and speciation, is the presence of heritable genetic variation that results in fitness differences. In the past, most changes in the genetic material were considered neutral or close to neutral because they occurred in noncoding DNA or resulted in a synonymous substitution. However, recent research suggests that many mutations in non-coding DNA do have slight deleterious effects.
But they can also give advantages! An example is intelligence and learning abilities?
Epigenetics is underlying the nurture effect. An example is how plants "remember" the length of the cold winter period in order to exquisitely time flowering so that pollination, development, seed dispersal and germination can all happen at the appropriate time. This requires an epigenetic longlasting 'memory', which explains how an organism can create a biological memory of some variable condition, such as quality of nutrition or temperature.They found that a key gene called 'Flowering Locus C' is either completely off or completely on in any one cell and also later in its progeny. They found that the longer the cold period, the higher the proportion of cells that have FLC stably flipped to the off position. This delays flowering and is down to a phenomenon known as epigenetic memory.
To provide experimental evidence to back up the model, the group used a technique where any cell that had the FLC gene switched on, showed up blue under a microscope. From  observations, it was clear that cells were either completely switched or not switched at all, in agreement with the theory.
They also showed that the histone proteins near the FLC gene were modified during the cold period, in such a way that would account for the switching off of the gene.
  • Andrew Angel, Jie Song, Caroline Dean, Martin Howard. A Polycomb-based switch underlying quantitative epigenetic memory. Nature, 2011; DOI: 10.1038/nature10241
The FTL gene was found in Arabidopsis research, one of the most extensively studied herbs. As instance here, Regulation of flowering in A. by an FTL homologue.
Reward sensory value-labelling, sleep connected to future expectations, etc. also requires some memory modulation.
Also stochastic resonance of different non-chemical forms? Stochastic resonance is a phenomenon that occurs in a threshold measurement system. This requires signals, and for plants light and carbon are signalling systems, also for animals the carbon signalling systems are real energetic entities, underlying the choise for the different molecular motors. See also the Negentropy Maximation Principle NMP in TGD.
The energy problem with too little available energy in biological ATP is maybe also partly solved?
See the short intro in earlier post.

söndag 11 november 2012

Methyldynamics behind virtually all pathologies?

A remarkable growth in the understanding of epigenetics and the impact of epigenetics on contemporary biology has occurred in recent years. This growth in the field of epigenetics has transformed our conceptualization of the impact of the environment upon our genes and upon our health. The nature and nurture relation is essential for function. Epigenetic modifications shape behavior, modulate stress responsivity, and alter immune function. This facet of epigenetics seeks to understand the interactive linkages that connect the psychological and social environment with the epigenetic processes that modulate gene expression and influence behavior. In a similar manner, the integrative field of psychoneuroimmunology continues to advance the understanding of the complex networks that connect brain, behavior and immunity. Stressors and/or adverse psychosocial environments can affect gene expression by altering the epigenetic patterns. The emphasis on genome itself is no longer particularly important. The dynamic modulations behind gene function are more interesting.

The Human Epigenome Project:  Methylation is the only flexible genomic parameter that can change genome function under exogenous influence. Hence it constitutes the main and so far missing link between genetics, disease and the environment that is widely thought to play a decisive role in the aetiology of virtually all human pathologies.

DNA expression is regulated by acetylation and deacetylation as a compression - expansion of the DNA chromatine. Also epigenetic factors are important for both  1) histone modulation and 2) arginine-lysine changes of DNA expansion (activation) /compression (inhibition), 3) and/or ncRNA expression. Both NO (from arginine) and histone deacetylase activity (HDAC; see next post) regulate gene expressions and the direction of other cellular processes. The biological influences achieved by various histone and DNA modifying enzymes eventually require that histone and DNA be modified in a highly dynamic way. Epigenetic modifications can be modulated by directly inhibiting modifying enzymes or blocking co-factor recruiting pathways, as instance. The best characterized 'erasers' are the histone deacetylases (HDACs). For a review of HDACs see (De Ruijter et al., 2003), but they are found for all categorizations of modulations.

DNA associates with histone proteins to form chromatin. From Wikipedia, epigenetics. A better figure is here.  A ribbon diagram of a nucleosome with central histones, their amino terminal tails, with DNA wrapped about the exterior surface. + short video of the DNA compression.

Epigenetics and Psychoneuroimmunology: Mechanisms and Models Mathews and Janusek 2010

In vertebrates, approximately 2 meters of DNA are contained within each cell and this DNA is packaged into chromatin in a manner that permits transcription of some loci and suppression of other loci. The basic unit of chromatin is the nucleosome, which is comprised of four core histones (H2A, H2B, H3, H4, two of each) around which 146 base pairs of DNA are wrapped.  The core histones are predominantly globular except for their amino terminal “tails,” which are unstructured. A striking feature of histones, and particularly of their tails, is the large number and types of amino acid residues that can be modified. These distinct types of modification include; acetylation, methylation, phosphorylation, ubiquitylation, sumoylation, deimination and proline isomerization (Kouzarides, 2007). Histones modification has been detected at over sixty different amino acid residues, but with extra complexity resulting from methylation at lysine or arginine residues that may be of three forms: mono-, di-, or trimethyl for lysines and mono- or di- (asymmetric or symmetric) for arginine. This vast array of modifications provide for enormous modification of functional responsivity.

The "epigenome" refers to the overall epigenetic state of a cell.  Epigenetic changes are preserved when cells divide, but mostly within one individual organism's lifetime, but, if gene disactivation occurs in a sperm or egg cell that results in fertilization, then some epigenetic changes can be transferred to the next generation. This raises the question of whether or not epigenetic changes in an organism can alter the basic structure of its DNA, a form of Lamarckism. This was in fact how the inherited epigenetic mechanism was detected by swedish scientists not so long ago. Diabetics and starvation as instance had herited effects, see the Överkalix study with Marcus Pembrey and colleagues.

The "epigenetic code"
could represent the total state of the cell; relevant forms of epigenetic information such as the histone code or direct DNA methylation patterns, or RNA modifications. The way that the cells stay differentiated in the case of DNA methylation is clearer to us than it is in the case of histone shape.

One  thinking is that this tendency of acetylation is associated with "active" transcription as biophysical nature. Because it normally has a positively charged nitrogen at its end, lysine can bind the negatively charged phosphates of the DNA backbone. The acetylation event converts the positively charged amine group on the side chain into a neutral amide linkage. This removes the positive charge, thus loosening the DNA from the histone. This is the "cis" model of epigenetic function. There is also a 'trans' function.
Although histone modifications occur throughout the entire sequence, the unstructured N-termini of histones (called histone tails) are particularly highly modified. These modifications include acetylation, methylation, ubiquitylation, phosphorylation and sumoylation. Acetylation is the most highly studied of these modifications.

Differing histone modifications are likely to function in differing ways; acetylation at one position is likely to function differently than acetylation at another position. Also, multiple modifications may occur at the same time, and these modifications may work together to change the behavior of the nucleosome. The idea that multiple dynamic modifications regulate gene transcription in a systematic and reproducible way is called the histone code

There are several layers of regulation of gene expression. One way that genes are regulated is through the remodeling of chromatin. If the way that DNA is wrapped around the histones changes, gene expression can change as well. Chromatin remodeling is accomplished through two main mechanisms:
  1. The first way is post translational modification of the amino acids that make up histone proteins, long chains of amino acids, and if they are changed, the shape of the histone sphere might be modified. DNA is not completely unwound during replication. It is possible, then, that the modified histones may be carried into each new copy of the DNA. Once there, these histones may act as templates, initiating the surrounding new histones to be shaped in the new manner. By altering the shape of the histones around it, these modified histones would ensure that a differentiated cell would stay differentiated, and not convert back into being a stem cell.
  2. The second way is the addition of methyl groups to the DNA, mostly at CpG sites, to convert cytosine to 5-methylcytosine. 5-Methylcytosine performs much like a regular cytosine, pairing up with a guanine. However, some areas of the genome are methylated more heavily than others, and highly methylated areas tend to be less transcriptionally active, through a mechanism not fully understood. Methylation of cytosines can also persist from the germ line of one of the parents into the zygote, marking the chromosome as being inherited from this parent (genetic imprinting). Certain enzymes  have a higher affinity for the methylated cytosine, and induce then more methylation. Hypermethylation typically occurs at CpG islands in the promoter region and is associated with gene inactivation. Global hypomethylation has also been implicated
The RNA World, = before gene regulation.
There is an RNA component, possibly involved in epigenetic gene regulation. Small interfering RNAs can modulate transcriptional gene expression via epigenetic modulation of targeted promoters.
Other epigenetic changes are mediated by the production of different splice forms of RNA, alternative splicing, see below,  or by formation of double-stranded RNA (RNAi). Descendants of the cell in which the gene was turned on will inherit this activity, even if the original stimulus for gene-activation is no longer present. These genes are most often turned on or off by signal transduction, although in some systems where syncytia or gap junctions are important, RNA may spread directly to other cells or nuclei by diffusion.

Alternative splicing modulation of the pyruvate kinase M gene involves a choice between mutually exclusive exons 9 and 10, writes Wang et al in Manipulation of PK-M mutually exclusive alternative splicing by antisense oligonucleotides, 2012. One alternative is crucial for aerobic glycolysis (the Warburg effect) and tumour growth. Splicing enhancer elements that activate exon 10 are mainly found in exon 10 itself, and deleting or mutating these elements increases the inclusion of exon 9 in cancer cells. The 'antisensing of oligonucleotides'-mediated switch in alternative splicing leads to apoptosis in glioblastoma cell lines, and this is caused by the downregulation of PK-M2,not from another kinase. Note that this are changes in RNA:s only, not genes, so there are a very rich RNA regulating world that we are mostly unaware of yet.

Emotions are strong modulators.
This excerpt links the exon modulations and signalling events in cells induced by motherly care first week after birth.
The exact mechanism whereby maternal LG behavior (L=low) influences methylation of the GR promoter is currently unknown. Yet a series of studies implicate the involvement of the transcription factor, nerve growth factor-inducible protein A (NGFI-A), which functions to transcribe the gene that encodes for GR in the hippocampus. It is proposed that NGFI-A, couples with other transcription factors, cyclic-AMP response element binding protein (CREB) and specific protein 1 (SP-1), to bind to the GR 5’ untranslated promoter exon 17. The binding of this complex of proteins has been theorized to contribute to the reconfiguring of the methylation pattern of GR promoter exon 17. The timing is critical in that this re-configuration of methylation is dependent upon levels of maternal LG during the first postnatal week (Weaver et al., 2004; Weaver et al., 2007). Following birth there is rapid de novo methylation of GR exon 17, which is then demethylated over the course of the first postnatal week. It is this postnatal demethylation that is regulated by maternal LG behavior.
  • Other chapters in this remarcable study: 
  • Epigenetic Perpetuation of Behavior Across Generations 
  • Child Abuse, Suicide, and Epigenetic Modification 
  • Prenatal Depression, Epigenetics and Infant Stress Response 
  • Maternal Separation Stress, AVP, and Epigenetics 
  • Early Life Adversity and Epigenetic Modification of BDNF Expression = Brain derived neurotrophic factor 
  • Stress-Induced Depression Models and Epigenetic Modification of BDNF 
  • Epigenetic Mechanisms in Aging-Associated Memory Impairment 
  • Resilience to Stress-Induced Depression and Epigenetics 
  • Stressor Duration and Epigenetic Modification 
  • Post Traumatic Stress Disorder and Epigenetics 

From the study: It is clear that epigenetic modifications (e.g. those described above) serve as the molecular basis for environmental signals that influence behavioral outcomes and, as such, provide a bridge between the psychosocial world and the biological. This is congruent with psychoneuroimmunology, which seeks to understand the impact of environmental stimuli, especially psychosocial stimuli, on behavior, emotions, neuroendocrine stress responsivity, and immune function. There is no doubt that the genome of an individual provides the blueprint for biological responsivity. However, the epigenome adds another layer ‘on top of the genome’ and serves to modulate gene expression in response to environmental cues. It is likely that the interconnectivity among brain, behavior, and immunity may in fact be directed epigenetically. How, when and where the genetic blueprint will be used in response to a particular stimulus will be a summation of biological networks within the individual. This will include not just DNA recognition events or transcriptional circuits but also the instruction for the use of the blueprint, by epigenetic responsivity that regulates ordered or disordered gene expression patterns. Given the focus of psychoneuroimmunology, epigenetic approaches are particularly appealing and, most importantly, consistent with the concept that brain, behavior and immunity are intimately linked and responsive to environmental context. Intriguing and emerging evidence implicates epigenetic modifications as mediators of psychosocial-biological effects and makes analysis of epigenetics/epigenomics essential to understanding the interconnections among those systems that represent the core of pyschoneuroimmunology. These epigenetic effects have been demonstrated to be related to forms of histone modification, DNA methylation and/or ncRNA expression for a variety of immune based diseases including; systemic lupus erythematosus and rheumatoid arthritis (Martino and Prescott, 2010; Trenkmann et al., 2010) type 1 diabetes, celiac disease and idiopathic thrombocytopenia (Brooks et al., 2010), multiple sclerosis (Lincoln and Cook, 2009), as well as asthma and allergy (Martino and Prescott, 2010; Handel et al., 2010). There have been suggestions that psychosocial distress may contribute to either the exacerbation or development of these diseases. It is therefore plausible that psychosocial distress may impact the immune system by epigenetic processes. Evolving evidence suggests that epigenetic modification may contribute to major psychoses and depression (Feinberg, 2010; Janssen et al., 2010) or obesity (Handel et al., 2010). Not all genes may be responsive or susceptible to epigenetic modification. Much of DNA is inaccessible within a cell and may not be responsive to environmentally induced chromatin remodeling signals (Fraser and Bickmore, 2007). For example, Weaver et al. found that infusion of an HDAC inhibitor into the adult rat hippocampus altered expression of only about 2% of all genes normally expressed (Weaver et al., 2006). It is possible that a relatively restricted pool of adult genes may be dynamically responsive to environmental cues. Certainly, it is unlikely that all genes can be modified through environmentally induced epigenetic processes. Future investigations will be challenged to link epigenetic modifications to functional changes in the expression of specific genes and moreover, to relate these changes to physiological and/or psychological outcomes. It is such linkages that are essential to draw meaningful conclusions as to the biological and health-relevant significance of epigenetic modification. It is unclear whether the evaluations of surrogate epigenetic marks in blood, saliva, and/or buccal swabs reflect such marks in other disease associated tissues. Epigenetic marks are tissue and cell specific, as well as dependent on stage of life and gender. In conclusion, it is likely that epigenetic patterns translate or at least contribute to the relationship between the environment and human health. This possibility opens wide a vista of potential interventions, including behavioral or dietary interventions that can take advantage of the plasticity of the epigenome (Handel et al., 2010).

Drug development has focused mainly on histone acetyltransferase (HAT) and histone deacetylase (HDAC). This is the reason for this short introduction. There are news about memory formation and synaptic plasticity. I wanted to put them in a context.

"Epigenetics, Brain, Behavior, and Immunity" gives a good overview of epigenetics  provided with a consideration of the nature of epigenetic regulation including DNA methylation, histone modification and chromatin re-modeling. Illustrative examples of recent scientific developments are highlighted to demonstrate the influence of epigenetics in areas of research relevant to those who investigate phenomena within the scientific discipline of psychoneuroimmunology. These examples are presented in order to provide a perspective on how epigenetic analysis will add insight into the molecular processes that connect the brain with behavior, neuroendocrine responsivity and immune outcome.

This is something pointed out also by Radoslav Bozov in his paper 'Theory of Carbon Signaling. Negentropy vs Entropy. Emergence of Self Propagated Biological Systems', with whom I have discussed much. See also my earlier posts Life is part of the environment, the molecular mechanisms of innate immunity, cancer not a result of mutations the informational problem - cell membrane and promoter - telomeres and loops. Also thanks to TGD.

torsdag 1 november 2012

First snow.

Can you make a snowball today, the kids wondered when the first snow fell? Oh, I'll try, surely mom can make a snowman, though nobody else can... and here he is. He lived in three days til the head dropped off. We tried to shelter it with a scarf and a cap.

And don't look at the background...
When I woke up this morning
from my slumber
I saw it clearly

My heart is like a cave
with the peculiar ability
to open wide up at occasions
and filled with diamonds, so bristling and shining
like Aladdins cave in the story.

Once a woman said to me
Oh, nice to meet you
such a beautiful soul
filled with light and angels around

I had to laugh at her
Me? Beautiful?
She must be kidding
I am just ordinary, common, clumpsy...
Another said, look at the cat!
She sees many light balls around
I just smiled

You must be something special, you said
but not necessarily in a positive tone

Nice, smooth aura, filled with yellow light, said an old woman
You said, there is a light around you
Oh, I wish I could see those things...

You should be writing, said one
so nice words
I know, I am so splitted
thousand things to do
thousand stories to tell
thousand humans to heal
thousand duties

Where do I start?
How would I find the inner peace to do it?
Listen to the heart, it is calling
and has called a long time already.

Some said, you have to follow your heart
or you will be seriously ill
I believe so.
Where your soul wander
there you have to follow.

This is my favourite, you said
look, a heart, from me
Oh, so beautiful
a cave opened up
filled with thousand bristling diamonds
the Aladdin cave?