fredag 26 december 2014

Is it possible to live without food or water for 70 years?

In the news are told about an Indian yogi that hasn't eaten or drank anything for 70 yeras. Is that a lie, simply bogus, or is it even possible? He claims he has not consumed any food or liquids since he was 8-years old. He also claims he left home when he was 7 to live as a wandering monk in the jungle, and to have been blessed at the age of 8 by a goddess. This allows him to survive without sustenance except for that which he derives from the practice of meditation. He claims that there is a hole in his palate through which his head drops nectar, giving him nutrition and enabling him to live without food or water...

This 'nectar' or 'elixir' is maybe something, but unknown so far. Head as manufacturer of nutrition is unheard, but in fact he has been examined under control and tested and is in very good health (better health than someone half his age, they say).
From April 22nd until  May 6th 2010 (then 83 years old) in the private hospital Sterling Hospital, Prahlad Jani was observed and tested by Sudhir Shah and a team of 35 researchers all from the Indian Defense Institute of Physiology and Allied Sciences (DIPAS) and other organizations.
Tests: 83-year-old Prahlad Jani has twice attended hospital to be watched by eminent doctors
The large team studied Jani daily using clinical examinations, blood tests, and scans. 24 hour CCTV surveillance was used to ensure the maximum observation of Jani’s actions during the testing period. According to researchers, the only time Jani was taken out of his sealed room was for tests and exposure to sun. During these times, continuous video recording was done to ensure authenticity of results. Jani only had contact with any form of liquid when he had an occasional bathing session, which first took place on day 5, and when he would gargle some water. It is important to note that his toilet was sealed to test his claims that he did not urinate or defecate.
After the fifteen days of intensive observation during which Jani did not eat, drink or go to the toilet, all medical test results came back as normal and doctors described his health as being better than someone half his age. Interestingly, doctors reported that although the amount of liquid in Jani’s bladder fluctuated and that Jani appeared “able to generate urine in his bladder”, he did not pass any urine. The reported levels of Jani’ leptin and ghrelin, two appetite-related hormones, suggested that Jani may be demonstrating an extreme form of adaptation to starvation and water restriction. Picture from Daily Mail. Blood tests, hormone profiles, MRIs and angiographs (imaging tests of the blood vessels) all pointed to the conclusion that Mr Jani had not needed to eat, drink or use the toilet once.
Dr Ilavazhagn said: ‘Clinical, biochemical, radiological and other relevant examinations were done on Prahlad Jani and all reports were within the safe range throughout the study. He is healthy, his mind is sharp.
Practitioners of extreme starvation diets can cause serious damage to their bodies, leading to death. And yet, despite all that is known, there is a growing bandwagon that says Mr Jani and his incredible claims should not be dismissed entirely out of hand. The doctors are considering only the two weeks during which Mr Jani was under their supervision. His claims not to have eaten for the preceding seven decades can and will never be verified. The same goes for much of his early history. Daily Mail:
When he reached the age of 11, he underwent a religious experience during which he became a follower of the Hindu goddess Amba. In her honour, he chose to dress as a female devotee, wearing a red sari-like garment, nose-ring, bangles and crimson flowers in his shoulder-length hair.  In return, Mr Jani believes that the goddess has sustained him ever since by feeding him with a lifegiving, invisible ‘elixir’, which has supposedly given him the strength to continue without food or water.  For at least the past 40 years, Mr Jani has been living, hermit-like, in a cave in the jungles close to the Gujarati temple of Ambaji. He rises at 4am, spending most of the day meditating. "Although I walk 100 or 200 kilometres in the jungle, I never sweat and don’t feel tired or sleepy," he says. "I can meditate for three, eight or 12 hours — or even months."
In 2003 he underwent his first hospital investigations. Then, as now, he was placed under the care of Dr Sudhir Shah, a consultant neurologist from Ahmedabad who specialises in studying people with seemingly ‘supernatural’ powers. While the results secured him an international following, they failed to offer any concrete answers. As a result, Dr Shah and the military team decided to repeat the experiment this year.
Dr Shah has been in charge of three similar investigations over the past ten years, and he has never allowed independent verification.
In 2000, he was asking for funds to investigate a man. Manek, he claimed got his energy from the sun, just like plants do.
In 2003, he even approached NASA for funds to investigate Mr Jani, claiming astronauts might benefit from the research. This particular hospital, led by this particular doctor, keeps on making these claims without ever producing evidence or publishing research.
The 2000 year study of Manek's fasting continuous for 411 days, as per jain tradition.(i.e. taking only boiled water during day time and just no other food or liquids) is published here. A hypothesis.
You will agree that such a prolonged continuous Jain fasting for religious (Spread of Ahimsa and other high mottos); scientific purposes (to create awarness about Sun-energy); also aimed at solution of four way human crisis (Physical, Mental, food; neurological) under scrupulous daily medical supervision is unheard of.
How does his energy mathematics work? they ask, and propose a hypothesis which has four basic steps
(1) Reducing calorie requirement by chronic adaptation (hibernation).
(2) Deriving basic energy from cosmic sources-chiefly, `sun energy'-solar energy (from environment, other humans).
(3) Utilizing the energy in the efficient way and recycling the same in his own body. 
(4) Genetically or phenotypically a different body disposition.
The method practiced by Manek : To look at the rising sun daily, with naked eye and without blinking the eyes, as far as possible. To look for a few seconds initially and then every week to increase by few few seconds to ultimately reach up to several minutes. Eyes and specially retina must be healthy.
They guess:
Through complex ways, distinct pathways this energy must enter the body. Is it a direct entry in to the physical body or it enters through auras (modulator) of human body. There is a pathway from the retina, to the hypthalamus, called the retinohypothalamic tract. This brings information about the dark  light cycles to supra chiasmatic nucleus (SCN) of the hypothalamus. From the SCN, impulses along the nerve travel via the pineal nerve (Sympathetic nervous system) to the pineal gland. These impulses inhibit the production of melatonin. When these impulses stop (at night or in dark, when the light no longer stimulates the hypothalamus) pineal inhibition caeses,  melatonin is released. The pineal gland (or the third eye ) is therefore a photosensitive organ  an important timekeeper.  This solar (light and heat) energy may be transformed into electrical, magnetic or chemical energies in body.

Janis study is here.

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?

fredag 8 juni 2012

Artificial atoms, mechanized molecules and synthetic chrystals.

Artificial atoms or Quantum dots.
Artificial atom is an object that has bound, discrete electronic states, as is the case with naturally occurring atoms. Semiconductor quantum dots are the most common example of artificial atoms, and are analogies for real atoms. Artificial atoms are made up of more than one atom, but are like single atoms in one important way: when you provide the right amount (or quanta) of energy, they will give off coloured light.

Programmable matter refers to matter which has the ability to change its physical properties (shape, density, moduli, optical properties, etc.) in a programmable fashion, based upon user input or autonomous sensing. Programmable matter is thus linked to the concept of a material which inherently has the ability to perform information processing. .
Programmable matter is a term originally coined in 1991 by Toffoli and Margolus to refer to an ensemble of fine-grained computing elements arranged in space. Their paper describes a computing substrate that is composed of fine-grained compute nodes distributed throughout space which communicate using only nearest neighbor interactions. In this context, programmable matter refers to compute models similar to cellular automata and Lattice Gas Automata. The CAM-8 architecture is an example hardware realization of this model. This function is also known as "digital referenced areas" (DRA) in some forms of self-replicating machine science.
1. The programming could be external to the material and might be achieved by the "application of light, voltage, electric or magnetic fields, etc.". For example, in this school of thought, a liquid crystal display is a form of programmable matter.
2. The individual units of the ensemble can compute and the result of their computation is a change in the ensemble's physical properties.
3.  Scale is one key differentiator between different forms of programmable matter. Nano - cm, and even bigger. At the nanoscale end of the spectrum there are a tremendous number of different bases for programmable matter, ranging from shape changing molecules to quantum dots or artificial atoms. In the micrometer to sub-millimeter range examples include claytronics, MEMS-based units, cells created using synthetic biology, and the utility fog concept.
"Simple" programmable matter see also Smart material.
 Materials that can change their properties based on some input, but do not have the ability to do complex computation by themselves.
1. The physical properties of several complex fluids can be modified by applying a current or voltage, as is the case with liquid crystals.
2.  Metamaterials are artificial composites that can be controlled to react in ways that do not occur in nature. One example developed by David Smith and then by John Pendry and David Schuri is of a material that can have its index of refraction tuned so that it can have a different index of refraction at different points in the material.
3.  Molecules that can change (mechanostereochemistry) their shape, as well as other properties, in response to external stimuli. Can be used individually or en masse, ex, molecules that can change their electrical properties as mechanized molecules,  mechanically-interlocked molecular architectures such as molecular Borromean rings, catenanes and rotaxanes utilizing molecular recognition and molecular self-assembly processes. These topologies can be employed as molecular switches and as motor-molecules, and even applied these structures in the fabrication of nanoelectronic devices and nanoelectromechanical systems (NEMS).
π–stack charachters have been applied to the DNA structure  too, as reductive  electron-transport system, and its oxidative hairpins for hole transfer through DNA. These interactions are important in base stacking of DNA nucleotides, protein folding and protein chrystal formation, template-directed synthesis, materials science, and molecular recognition, Despite intense experimental and theoretical interest, there is no unified description of the factors that contribute to pi stacking interactions. There are compelling computational evidence for the importance of direct interaction in pi stacking. It  seems that the relative contributions of electrostatics, dispersion, and direct interactions to the substituent effects seen in pi stacking interactions are highly dependent on geometry and experimental design. The chromophore has also a special role, and it has been linked to quantum biology. see Mechanisms for DNA charge transport..

Self-Reconfiguring Modular Robotics is a field of robotics in which a group of basic robot modules work together to dynamically form shapes and create behaviours suitable for many tasks. Like Programmable matter SRCMR aims to offer significant improvement to any kind of objects or system by introducing many new possibilities for example:
1. Most important is the incredible flexibility that comes from the ability to change the physical structure and behavior of a solution by changing the software that controls modules.
2. The ability to self-repair by automatically replacing a broken module will make SRCMR solution incredibly resilient.
3. Reducing the environmental foot print by reusing the same modules in many different solutions.

Claytronics,  nanoscale robots ('claytronic atoms', or catoms) designed to form much larger scale machines or mechanisms. The catoms will be sub-millimeter computers that will eventually have the ability to move around, communicate with other computers, change color, and electrostatically connect to other catoms to form different shapes.

Quantum wells, a potential well with only discrete energy values, can hold one or more electrons. Those electrons behave like artificial atoms which, like real atoms, can form covalent bonds, but these are extremely weak. Because of their larger sizes, other properties are also widely different. One way to create quantization is to confine particles, which were originally free to move in three dimensions, to two dimensions, forcing them to occupy a planar region. The effects of quantum confinement take place when the quantum well thickness becomes comparable to the de Broglie wavelength of the carriers (generally electrons and holes), leading to energy levels called "energy subbands", i.e., the carriers can only have discrete energy values. Quantum wells are formed in semiconductors by having a material, like gallium arsenide sandwiched between two layers of a material with a wider bandgap, like aluminium arsenide. These structures can be grown by molecular beam epitaxy or chemical vapor deposition with control of the layer thickness down to monolayers. Thin metal films can also support quantum well states, in particular, metallic thin overlayers grown in metal and semiconductor surfaces. The electron (or hole) is confined by the vacuum-metal interface in one side, and in general, by an absolute gap with semiconductor substrates, or by a projected band gap with metal substrates.

Synthetic biology aims to engineer cells with "novel biological functions." Such cells are usually used to create larger systems (e.g., biofilms) which can be "programmed" utilizing synthetic gene networks such as genetic toggle switches, to change their color, shape, etc. Protocells and other minimal solutions.
Construction of a chemical system capable of replication and evolution, fed only by small molecule nutrients, is now conceivable. This could be achieved by stepwise integration of decades of work on the reconstitution of DNA, RNA and protein syntheses from pure components. Such a minimal cell project would initially define the components sufficient for each subsystem, allow detailed kinetic analyses and lead to improved in vitro methods for synthesis of biopolymers, therapeutics and biosensors. Completion would yield a functionally and structurally understood self-replicating biosystem. Safety concerns for synthetic life will be alleviated by extreme dependence on elaborate laboratory reagents and conditions for viability. Our proposed minimal genome is 113 kbp long and contains 151 genes. We detail building blocks already in place and major hurdles to overcome for completion.
 An external file that holds a picture, illustration, etc.
Object name is msb4100090-f1.jpg Object name is msb4100090-f1.jpg A minimal cell containing biological macromolecules and pathways proposed to be necessary and sufficient for replication from small molecule nutrients. 

See also

Quantum dots are like man-made, detected 1980,  artificial atoms that are described by discrete states.
It is a portion of matter (e.g., semiconductor) whose excitons are confined in all three spatial dimensions. Consequently, such materials have electronic properties intermediate between those of bulk semiconductors and those of discrete molecules. They could only be used in low temperature settings earlie, but this new technology described in Science Daily does not. Quantum dots have previously ranged in size from 2-10 nanometers in diameter.  While typically composed of several thousand atoms, all the atoms pool their electrons to “sing with one voice”, that is, the electrons are shared and coordinated as if there is only one atomic nucleus at the centre.

As with any crystalline semiconductor, a quantum dot's electronic wave functions extend over the crystal lattice. Similar to a molecule, a quantum dot has both a quantized energy spectrum and a quantized density of electronic states near the edge of the band gap. The quantum dot absorption features correspond to transitions between discrete,three-dimensional particle in a box states of the electron and the hole, both confined to the same nanometer-size box.These discrete transitions are reminiscent of atomic spectra and have resulted in quantum dots also being called artificial atoms.
Its electronic characteristics are closely related to the size and shape of the individual crystal. Generally, the smaller the size of the crystal, the larger the band gap, the greater the difference in energy between the highest valence band and the lowest conduction band becomes, therefore more energy is needed to excite the dot, and concurrently, more energy is released when the crystal returns to its resting state. A main advantage with quantum dots is that, because of the high level of control possible over the size of the crystals produced, it is possible to have very precise control over the conductive properties of the material. Quantum dots of different sizes can be assembled into a gradient multi-layer nanofilm.

 Quantum Dots
The National Institute of Nanotechnology at the University of Alberta announced that they created the smallest quantum dot, 2009. From What's the spin on quantum dots.

In a semiconductor crystal lattice, the electrons are squeezed together, since no two nearby electrons can share exactly the same energy level according to Pauli exclusion principle, leading to quantum confinement. The energy level can then be modeled using particle in a box, which leads to the conclusion that the energy levels of the quantum dot is dependent on its size. When the size of the quantum dot is smaller than the critical characteristic length called the Exciton Bohr radius, the electrons crowding lead to the splitting of the original energy levels into smaller ones with smaller gaps between each successive level. The Exciton Bohr radius is larger than the Bohr radius due to the effect of dielectric screening and the influence of periodic lattice structure of the crystal. The quantum dots that have radii larger than the Exciton Bohr radius are said to be in the 'weak confinement regime' and the ones that have radii smaller than the Exciton Bohr radius are said to be in the 'strong confinement regime'. Thus, if the size of the quantum dot is small enough that the quantum confinement effects dominate(typically less than 10 nm), the electronic and optical properties change, and the fluorescent wavelength is determined by the size.

3D confined electron wave functions in a quantum dot. Here, rectangular and triangular-shaped quantum dots are shown. Energy states in rectangular dots are more s-type and p-type. However, in a triangular dot the wave functions are mixed due to confinement symmetry.

Besides confinement in all three dimensions (i.e., a quantum dot), other quantum confined semiconductors include:
  • Quantum wires, which confine electrons or holes in two spatial dimensions and allow free propagation in the third.
  • Quantum wells, which confine electrons or holes in one dimension and allow free propagation in two dimensions. Wells can be of many kinds.
Different sized quantum dots emit different color light due to quantum confinement.

The images in this series represent the electron densities in a quantum dot artificial atom.
Quantum Dot Wave Function  (Image 1)

Part of a series of images depicting electron densities in a quantum dot artificial atom

The visuals were generated by the nanoelectronic modeling tool called NENO 3-D, and were visualized on the nanoVIS rendering service at, a rich, Web-based resource for research, education and collaboration in nanotechnology. was created by the National Science Foundation (NSF)-funded Network for Computational Nanotechnology (NCN), a network of universities with a vision to pioneer the development of nanotechnology, from science to manufacturing, through innovative theory, exploratory simulation and novel cyberinfrastructure. NCN students, staff and faculty are developing the NanoHUB science gateway, while making use of it in their own research and education. Collaborators and partners across the world have joined NCN in this effort.

NanoHUB hosts over 790 resources to help users learn about nanotechnology, including online presentations, courses, learning modules, podcasts, animations, teaching materials and more. Most importantly, NanoHUB offers simulation tools that can be accessed from your Web browser, so you can not only learn about, but also simulate nanotechnology devices. NanoHUB also provides collaboration environment via Workspaces, online meetings and user groups.

 (Date of Image: May 2006)  Image 2.
 Part of a series of images depicting electron densities in a quantum dot artificial atom
Part of a series of images depicting electron densities in a quantum dot artificial atom
Image 3
Credit: Wei Qiao, David Ebert, Marek Korkusinski, Gerhard Klimeck; Network for Computational Nanotechnology, Purdue University

Download the high-resolution JPG version of the image. (399 KB
Use your mouse to right-click (Mac users may need to Ctrl-click) the link above and choose the option that will save the file or target to your computer.

Synthetic chrystals.
Element Six, the world leader in synthetic diamond supermaterials, working in partnership with academics in Harvard University, California Institute of Technology and Max-Planck-Institut für Quantenoptik, has used its Element Six single crystal synthetic diamond grown by chemical vapour deposition (CVD) to demonstrate the capability of quantum bit memory to exceed one second at room temperature.

Using synthetic diamond, Element Six and Harvard University have set a new room temperature quantum information storage record of more than one second – a thousand times longer than previously recorded.

It proved the ability of synthetic diamond to provide the read-out of a quantum bit which had preserved its spin polarisation for several minutes and its memory coherence for over a second. This is the first time that such long memory times have been reported for a material at room temperature, giving synthetic diamond a significant advantage over rival materials and technologies that require complex infrastructure which necessitates, for example, cryogenic cooling.

The versatility, robustness, and potential scalability of this synthetic diamond system may allow for new applications in quantum information science and quantum based sensors used, for example, in nano-scale imaging of chemical/biological processes.

Steve Coe, Element Six Group Innovation Director, explained the success of the collaboration:

"The field of synthetic diamond science is moving very quickly and is requiring Element Six to develop synthesis processes with impurity control at the level of parts per trillion – real nano-engineering control of CVD diamond synthesis. We have been working closely with Professor Lukin's team in Harvard for three years - this result published in Science is an example of how successful this collaboration has been."

Professor Mikhail Lukin of Harvard University's Department of Physics described the significance of the research findings:

"Element Six's unique and engineered synthetic diamond material has been at the heart of these important developments. The demonstration of a single qubit quantum memory with seconds of storage time at room temperature is a very exciting development, which combines the four key requirements of initialisation, memory, control and measurement. These findings might one day lead to novel quantum communication and computation technologies, but in the nearer term may enable a range of novel and disruptive quantum sensor technologies, such as those being targeted to image magnetic fields on the nano-scale for use in imaging chemical and biological processes."

The findings represent the latest developments in quantum information processing, which involves manipulating individual atomic sized impurities in synthetic diamond and exploiting the quantum property spin of an individual electron, with superposition so this quantum spin (qubit) can be both 0 and 1 simultaneously. It is this property that provides a framework for quantum computing, but also for more immediate applications such as novel magnetic sensing technologies.

See also  About protons and atoms.

onsdag 6 juni 2012

Quantum Biology.

Photosynthetic quantum mechanism.


Morphogenetic fields. Short.


Dendritic cytoskeleton.

Electronics of benzoediazepins.

Quantum Biology and the Hidden Nature of Nature
John Hockenberry, Paul Davies, Seth Lloyd, Thorsten Ritz 

The Kaye Playhouse at Hunter College

Chromatophores etc.  World Science Festival 2012. Can the spooky world of quantum physics explain bird navigation, photosynthesis and even our delicate sense of smell? Clues are mounting that the rules governing the subatomic realm may play an unexpectedly pivotal role in the visible world. Leading thinkers in the emerging field of quantum biology explored the hidden hand of quantum physics on the scales of everyday life.
Thorsten Ritz is a biophysicist interested in the role of quantum mechanics in biological systems, ranging from photosynthetic light harvesting systems to sensory cells. He has championed the idea that a quantum mechanical reaction may lie at the heart of the magnetic compass of birds and other animals. Straddling and often breaking the barriers between theory and experiment and physics and biology, he has worked with biologists to provide the first experimental evidence supporting a quantum-based compass in birds.
He is currently an associate professor of physics and astronomy at the University of California, Irvine. His work has received national and international recognition, including awards from the Royal Institute of Navigation (UK), Institute of Physics (UK), American Physical Society, Alfred P. Sloan Foundation, and the Research Cooperation.

Working with a variety of groups to construct and operate quantum computers and quantum communication systems, Seth Lloyd is the first person to develop a realizable model for quantum computation. His research focuses on the role of information in complex systems and the quantum mechanics of living systems (known as `quantum life’), economics, and cosmology.
Lloyd is the author of over a hundred scientific papers, including the publication Programming the Universe. He is currently the professor of quantum-mechanical engineering at MIT and the director of the W.M. Keck Center for Extreme Quantum Information Theory.

Paul Davies is a theoretical physicist, cosmologist, astrobiologist and best-selling author. He is Regents’ Professor at Arizona State University, where he directs the Beyond Center for Fundamental Concepts in Science—a cosmic think tank that tackles the big questions of existence, from the origin of the universe to the origin of life and the nature of time. Davies also directs a National Cancer Institute research program that studies cancer from a physics perspective. Among his research accomplishments, he has helped explain how black holes radiate energy, what caused the ripples in the cosmic afterglow of the big bang, and why life on Earth may have come from Mars.
Davies has written about 30 books, most recently The Eerie Silence: Are We Alone in the Universe? His preoccupation with deep conceptual problems and his fearless championing of bold new ideas earned Davies the epithet of “The Disruptor” in a recent profile in Nature magazine. His many media projects include presenting two six-part series on “The Big Questions” for Australian television. He has received awards from The Royal Society and the UK Institute of Physics, and also received the 1995 Templeton Prize. In 2007 he was named a Member of the Order of Australia in the Queen’s birthday honors list.