onsdag 23 maj 2012

The “metabolic mystery.”

Dana foundation has a blogpost  The Brain’s Metabolic Mysteries where she talks of  the odd featre that 'less is more' regarding nutrients, what Charles Mobbs calls the “metabolic mystery”. He studies  the basic mechanisms by which hypothalamic neurons sense and regulate metabolic state (including body weight and food intake), and how these mechanisms are impaired in metabolic diseases and during aging. A driving question of our laboratory is what may be called the metabolic mystery. This refers to the fascinating phenomenon that obesity is a risk factor for most age-related diseases and indeed for mortality, and conversely dietary restriction appears to slow down the aging process and extend maximum lifespan.  
This has been shown so many times, also for plants, and is linked to immunity and health.
More restrictive diets result in a complicated (and counterintuitive) cascade of protective effects, preventing aging-related diseases and ultimately prolonging life. Fasting (intermittent, one day on, one day off, or even one day a week off food) and regular exercise may help promote optimal brain health in aging adults.

So food is not such a limiting factor for living, but quite the opposite? Mobb: 
almost all major pathologies are influenced by caloric intake, the mechanisms underlying the metabolic mystery may be considered among the most compelling in biomedical science. Why would caloric intake should lead to diseases?
We have thus begun to define a "nutritional field" of neurons which contain overlapping domains sensitive to different nutrients and which regulate different aspects of metabolism. Of particular interest is that the maximum overlap of these nutritional stimulation (e.g., glucose and leptin) may occur within the POMC neurons, which we now believe play a critical role in regulating metabolism. This is particularly interesting because the POMC neurons are among the most sensitive to decline during aging.

Mark Mattson.  “And what we’re thinking, from the standpoint of evolution, is that animals living in the wild, including our ancestors, often had to go extended time periods without food.  If you haven’t had food for a while, your mind becomes more active—it has to become very active, to help you figure out how to find food.
Normal ageing is accompanied by alterations in neuronal calcium handling and changes in lipid peroxidation, leading to increased generation of reactive oxygen species (ROS) and damage to mitochondria. These changes are permissive or instructive for the suppression of adult neurogenesis beginning in middle age. Successful ageing is characterized by the implementation of alternative plasticity mechanisms to compensate for changes in the local microenvironment. Age-related pathologies such as Alzheimer's disease, Parkinson's disease and Huntington's disease arise from a combination of genetic and environmental factors, but each disease shares a common feature in that age is a risk factor for disease onset. In this respect, ageing sets the stage for the onset of pathology.
"Give bread and theatre to the masses", said the Roman Emperors. The full stomach made people easier to handle. It is certainly valid today too. Never before has so many people been so overweighted. And we struggle to pay the health care bill. But very little money are directed to this research about the foundations of health.

Stress is good?
Fasting is a challenge, a stress, so we get focus on the stress-proteins, the chaperones, enzyme-like proteins that assist in folding or unfolding and the assembly or disassembly of other macromolecular structures. That is energy-transfer, neutralizing energy by relaxation/compression? Many chaperones are heat shock proteins, that is, proteins expressed in response to elevated temperatures or other cellular stresses. Stress makes more heat? Chaperones are membrane bound (ER) usually.

Why is stress good? So many times we have heard it is only bad. But stress is about everything that makes us living, the homeostasis is governed by stress. Without stress we would be dead. The body also handles challenges by producing more stress, in the allostasis. So...

That activity manifests itself in neuroplasticity, says Mattson. Plasticity is flexibility due to more stress? More swing in the system?
The manner in which experience can influence the synaptic organization of the brain is also the basis for a number of theories of brain function including the general theory of mind and epistemology referred to as Neural Darwinism and developed by immunologist Nobel laureate Gerald Edelman. The concept of neuroplasticity is also central to theories of memory and learning that are associated with experience-driven alteration of synaptic structure and function in studies of classical conditioning in invertebrate animal models such as Aplysia. This latter program of neuroscience research has emanated from the ground-breaking work of another Nobel laureate, Eric Kandel.
 Thinking (the talk cure) can change the brain, as meditation too. Stress copying is the essential tool in handling stress. It sits between the ears, not in what you actually have to do, I often say.

"Perhaps we eat to get information, negentropic entanglement. This explains why the metabolic energy must come from biomatter and we cannot get it by putting plug in the wall!", says Matti Pitkänen. Folding and molecule sort and size, as instance? Eating as a 'sampling' of our environment?

Linked to oxidative stress, says Mattson.  "Those protective effects result in the upregulation of brain-derived neurotrophic factor (BDNF) as well as anti-oxidants, DNA-repair enzymes, and other gene products that help promote plasticity and survival of neurons over time." BDNF is made on ER.
Exercise and caffeine imroves the levels too.  In 2009, variants close to the BDNF gene were found to be associated with obesity. Caffeine is  linked to diabetics too (diminish the stress). And linked to many other (stressinduced?) diseases.

Neurotrophin is also linked to regeneration (stem cells) and the DC-fields in our tissues, as explained by Robert Becker in his NEJ (neural epidermic junction) as a result of a 'signal of injury' and necessary for the healing process. Neurotrophins may be the chemical analog? They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow. They act on Trk-receptors, a family of tyrosine kinases that regulates synaptic strength and plasticity. The common ligands of trk receptors are neurotrophins which are growth factors. Another receptor is p75, which affects the binding affinity and specificity of Trk receptor activation by neurotrophins.

Mechanism of action.
BDNF binds at least two receptors on the surface of cells that are capable of responding to this growth factor, TrkB (pronounced "Track B") and the LNGFR (for low-affinity nerve growth factor receptor, also known as p75). It may also modulate the activity of various neurotransmitter receptors, including the Alpha-7 nicotinic receptor.
TrkB is a receptor tyrosine kinase (meaning it mediates its actions by causing the addition of phosphate molecules on certain tyrosines in the cell, activating cellular signaling). There are other related Trk receptors, TrkA and TrkC. Also, there are other neurotrophic factors structurally related to BDNF: NGF (for Nerve Growth Factor), NT-3 (for Neurotrophin-3) and NT-4 (for Neurotrophin-4). While TrkB is the primary receptor for BDNF and NT-4, TrkA is the receptor for NGF, and TrkC is the primary receptor for NT-3. NT-3 binds to TrkA and TrkB as well, but with less affinity (thus the caveat "primary receptor").
The other BDNF receptor, the p75, plays a somewhat less clear role. Some researchers have shown that the p75NTR binds and serves as a "sink" for neurotrophins. Cells that express both the p75NTR and the Trk receptors might, therefore, have a greater activity, since they have a higher "microconcentration" of the neurotrophin. It has also been shown, however, that the p75NTR may signal a cell to die via apoptosis; so, therefore, cells expressing the p75NTR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.
Neurotrophin and Trk receptors are linked to stochastic resonance, which can be used as a therapeutics in treatment of neuropsychiatric diseases.

Then I read about chaperones:
The common perception that chaperones are concerned primarily with protein folding is incorrect. The first protein to be called a chaperone assists the assembly of nucleosomes from folded histones and DNA and such assembly chaperones, especially in the nucleus, are concerned with the assembly of folded subunits into oligomeric structures.
And is also linked to phantom limbs, which is strangely common, occurring in 60-80% of amputees. Treatment approaches have included drugs such as antidepressants, Spinal cord stimulation, Vibration therapy, acupuncture, hypnosis, and biofeedback. Typical stochastic resonance theraphy? Phantom limb pain (rather than referred sensations) is the perceptual correlate of cortical reorganization.

Maps are topological and hierarchial microsystems of the body.

Well, now this gets interesting!

Stress used as medicine? WOW. And stochastic resonance is linked to tryptophan and serotonine. Pain relief is linked to breakdown of serotonin. Tryptophan is outside the nerves, serotonine inside. Like a polarization, also linked to stochastic resonance.

In fact acupuncture too works by inducing a strain on the tissue, we must achive damage or injury before we can get some emergency actions. Acupuncture effect is linked to adenosine Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture by Nanna Goldman and collaborators.  
We found that adenosine, a neuromodulator with anti-nociceptive properties, was released during acupuncture in mice and that its anti-nociceptive actions required adenosine A1 receptor expression. Direct injection of an adenosine A1 receptor agonist replicated the analgesic effect of acupuncture. Inhibition of enzymes involved in adenosine degradation potentiated the acupuncture-elicited increase in adenosine, as well as its anti-nociceptive effect. These observations indicate that adenosine mediates the effects of acupuncture and that interfering with adenosine metabolism may prolong the clinical benefit of acupuncture. 
This works against stress created by stochastic resonance. Acupuncture is balancing the homeostasis, as said by therapists. Is there a difference between outer and inner stress?

Also, CNS and perifer nerves does not work in the same way, shown by Alexander Presman with  “Electromagnetic Fields and Life” long ago (1970). From this scientific angle Presman found that the seemingly contradictory results started to make sense, and that the empirical data made up a rational whole. The information content of electromagnetic radiation is determined by its frequency, frequency range, coherence, pulse form, polarization and modulation. The biological effects of such kinds of electromagnetic fields will, according to Presman, affect three different levels of biological organisation:
1.      Effects on the physiological regulation of vital functions.
2.      Effects on the transmission of biological information within the organism and its internal regulation and co-ordination.
3.      Effects on the interaction between living beings and in the social interplay between them.
  (I have the book, here a link from Norwegian dr, Wilhelm Schelderup).

In CNS endorphins are produced by acupuncture-stress-injury. Endorphins deactivates the brains pain-processing. Note that pain and pleasure centers are side by side in brain. So there needs to be just a shift? "Activation of brain areas involved in pain perception was significantly reduced or modulated under acupuncture," Dr. Nina Theysohn said in “Acupuncture Changes Brain's Perception and Processing of Pain”. During the fMRI sessions, scientists captured pictures of the brain while patients were exposed to an external pain stimulus. The interesting part? The obtained data revealed that significantly reduced was not only the pain perception, but the patient's expectation of pain, too.

Functional magnetic resonance (fMR) images showing brain activity during electrical pain stimulation at the left ankle. Parts of the so-called "pain matrix" are activated: (a) primary somatosensory cortex (S1), (b) right insula, (c) precuneus, (d) left insula. (Credit: Image courtesy of Radiological Society of North America). 

fMRI was shown by Jie Tian to make "a dynamic reconfiguration of  complex neural networks." in "Acupuncture Effects measured by fMRI" p 8.  Earlier the focus in research was on acute effects, but the effects may peak long after the treatment is finished. So then the mechanism was missed? And the responses are functional, not spatial. Acupoints can have converging effects, as instance, that spatially overlap the posterior cingulate cortex/precuneus or encoding center. The delayed correspondence between visual acupoints (GB37, BL60) - but not the non-visual acupoints (KI8) - and the intrinsic visual networks via the encoding center indicated a temporal-spatial encoding mechanism underlying the sustained effects of acupuncture, he said. Different resource distribution in spatial and temporal domains. Mars 2011.

Pain relief as a superposition or 'negative negentropy' (not entropy)? By growing fields that lay the pain-field in the 'shadow'?

But DC-currents are not 'generated', Langevin showed the energy came from the connective tissue that acts as a storage of energy in its helical structure, just as DNA do.

The energy link is ATP/AMP/adenosine receptors, linked to stochastic noise. Maybe the needles create noise by relaxing (=unwinding the helix) the tissue, the 'signal of injury', and that starts ther process? So Becker and biochemists measure the same thing with different tools? The energy is simply transferred to ATP from connective tissue? And ATP is quantal?

Note also that pain and pleasure areas are side by side in brain, modulated by N. trigeminus, as Antonio Damasio showed. It has a very strong 'field'. Mortons headache is the worst possible.
The link to adaptation by stressproteins makes the mechanism delayed, and incorporates the time-aspect.

Adenosine, a natural compound known for its role in regulating sleep, for its effects on the heart, and for its anti-inflammatory properties. But adenosine also acts as a natural painkiller, becoming active in the skin after an injury to inhibit nerve signals and ease pain in a way similar to lidocaine.

Wikipedia: In humans, there are four types of adenosine receptors. Each is encoded by a separate gene and has different functions, although with some overlap. For instance, both A1 receptors and A2A play roles in the heart, regulating myocardial oxygen consumption and coronary blood flow, while the A2A receptor also has broader anti-inflammatory effects throughout the body. These two receptors also have important roles in the brain, regulating the release of other neurotransmitters such as dopamine and glutamate while the A2B and A3 receptors are located mainly peripherally and are involved in processes such as inflammation and immune responses.
Most older compounds acting on adenosine receptors are nonselective, with the endogenous agonist adenosine being used in hospitals as treatment for severe tachycardia (rapid heart beat), and acting directly to slow the heart through action on all four adenosine receptors in heart tissue, as well as producing a sedative effect through action on A1 and A2A receptors in the brain. Xanthine derivatives such as caffeine and theophylline act as non-selective antagonists at A1 and A2A receptors in both heart and brain and so have the opposite effect to adenosine, producing a stimulant effect and rapid heart rate. These compounds also act as phosphodiesterase inhibitors, which produces additional anti-inflammatory effects, and makes them medically useful for the treatment of conditions such as asthma, but less suitable for use in scientific research.
Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive research into the effects of blocking or stimulating the individual adenosine receptor subtypes, which is now resulting in a new generation of more selective drugs with many potential medical uses. Some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have also discovered many selective adenosine receptor ligands that are entirely structurally distinct, giving a wide range of possible directions for future research.
On Mattis blog:

And I wonder if the nerve loop take a turn outside the body too? It must get the information through communication. How would a model look like where there is no definite boundary? I don't think of the magnetic body now.

Stochastic resonance (from outer world) must be important. Take a locked-in patient with no dopamine and no communication with outer world, nor her inner self.

This can be a big piece in the puzzle. Thanks for bringing my attention here once again. Now the real happenings begins to be seen. Endorphin acts by deactivating brain areas and modulating, through intervention with the energy transport. But are the fields made bigger (=erasing?), so they create superposition, and that's the mechanism of modulation? Dopamine is the 'arousing' media (SR), creating oscillations of energy and coherence or decoherence giving actions (connects to outgoing loop?)? This is seen in the CREATION of disease?  Serotonin is the pain-producing media (inner SR?)?
See 'Quantum Model for the DC of Becker'.

A stress-pill?
Some studies suggested that caloric restriction promoted good health - and researchers have seen improved outcomes in animal models of Alzheimer’s disease, Parkinson’s disease, stroke and Huntington’s disease, but the intermittent fasting increases neurogenesis while limited daily reduction in calories has very little effect, say Mattson. Ye, increasing the swung?
we have now shown that transgenic enhancement of neuronal POMC will completely correct the diabetes and other impairments in genetically obese mice. These studies have led to discovery of a new class of anti-obesity drugs that we are now studying.
Ketogenic diet low.carb diet also reverse effects of high caloric diets? "We assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes" .So much that medicines act exactly as ketogenic diet. And doctors that almost forbid the patients to eat ketogenic. "Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined." What is so special with carbohydrates and carbon as a foundation of life, is the automatic question? How can avoiding carbon give health? What about vegetarians, they are seldom fat? Mobb:  
We have discovered over 20 novel genes that regulate obesity in C. elegans and a transcriptional complex that mediates the protective effects of dietary restriction to increase lifespan and protect against age-related diseases, including Alzheimer-type pathology and diabetic complications. Pharmacological activation of this pathway increases lifespan and protects against neurodegenerative diseases, and the same complex predicts lifespan and obesity in mice. We have now also developed novel high-throughput methods to discover novel anti-obesity and anti-diabetes drugs, and have discovered over 20 drugs in each class so far.
  •  Mizuno TM, Bergen H, Funabashi T, Kleopoulos SP, Zhong YG, Bauman WA, Mobbs CV. Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet- induced) and genetic (yellow agouti) obesity. Proc Natl Acad Sci U S A 1996; 93(8): 3434-3438.
  • Poplawski MM, Mastaitis JW, Isoda F, Grosjean F, Zheng F, et al. (2011) Reversal of Diabetic Nephropathy by a Ketogenic Diet. PLoS ONE 6(4): e18604. doi:10.1371/journal.pone.0018604
Medicalisation of something completely natural? So the health care bill can grow! Why do we have to go this way? Physicians and scientists on the faculty of Mount Sinai School of Medicine often interact with pharmaceutical, device and biotechnology companies...

Endorphins gives also a stress-reaction. In Acupuncture and Endorphins, by Han JS. 2004:
Studies on the mechanisms of action have revealed that endogenous opioid peptides in the central nervous system play an essential role in mediating the analgesic effect of EA[electroacupuncture]. Further studies have shown that different kinds of neuropeptides are released by EA with different frequencies. For example, EA of 2 Hz accelerates the release of enkephalin, beta-endorphin and endomorphin, while that of 100 Hz selectively increases the release of dynorphin. A combination of the two frequencies produces a simultaneous release of all four opioid peptides, resulting in a maximal therapeutic effect.
Local activation of adenosine A1 receptors by acupuncture needles in mice contributes to the anti-nociceptive effects of acupuncture.

Can different neuromodulators act as a cascade of frequencies, modulating our 'consciousness' through creation of flux tubes, in different ways (bigger/smaller). This we so often mix with our awareness of things and our intelligence. Intuition is also a form of intelligence?

"The efficiency of somatic energy metabolism is correlated with cognitive change over the lifespan. This relationship is bidirectional", says Alexis Stranahan and Mark Mattson in Bidirectional metabolic regulation of neurocognitive function. Cognition and metabolism are intertwined and interdependent.  Exercise and dietary energy restriction enhance cognition and improve metabolism.  Diabetes induces memory deficits and impairs metabolism.  Changes in immune function occur in metabolically enhanced or compromised states. The metabolic spectrum regulates the onset and extent of neuropathology.

Memory in the Body is a reality? It is seen in so many therapies, and is a basic prediction of TGD. Note also that caffeine diminish stress, so memory is a form of stress-energy? Metabolism is important. Note also that the main purpose of the blood-brain barrier in the brain is to create different metabolism for the brain, AND different polarizations, as shown by Becker. This is the basis for our 'consciousness'?

A typical glutamatergic neuron in the hippocampus is depicted receiving excitatory inputs (red) from neurons activated in response to exercise, cognitive challenges and dietary energy restriction. Examples of seven different adaptive stress response signalling pathways that protect neurons against degeneration and promote synaptic plasticity are shown. During exercise and cognitive challenges, postsynaptic receptors for glutamate (a,b), serotonin (c) and acetylcholine (d) are activated to engage intracellular signalling cascades and transcription factors that induce the expression of neuroprotective proteins including brain-derived neurotrophic factor (BDNF), mitochondrial uncoupling proteins (UCPs) and anti-apoptotic proteins (for example, BCL-2). BDNF promotes neuronal growth, in part, by activating mammalian target of rapamycin (mTOR). Mild cellular stress resulting from reduced energy substrates (e) and reactive oxygen species (ROS) (f) engages adaptive stress response pathways, including those that upregulate antioxidant enzymes (AOEs) and protein chaperones. Release of GABA from interneurons (g) in response to activity in excitatory circuits (as occurs during exercise and cognitive challenges) hyperpolarizes excitatory neurons protecting them from Ca2+ overload and excitotoxicity. CaMKII, calcium/calmodulin kinase II; CREB, cyclic AMP response element-binding protein; DAG, diacylglycerol; FOXO3, forkhead box protein O3; HO1, haem oxygenase 1; HSF1, heat shock factor 1; IP3 PKC, inositol-trisphosphate 3 protein kinase C; MnSOD, manganese superoxide dismutase; NF-κB, nuclear factor-κB; NQO1, NAD(P)H-quinone oxidoreductase 1; NRF2, nuclear regulatory factor 2; Ph2E, phase 2 enzyme; PMRS, plasma membrane redox system; SIRT, sirtuin.

But how many ways are there? We have five senses for input, or six, or seven, eight... if we also count the environmental input in stochastic resonance?
And how many for outputs?

PS. This text is still a bit premature, but I still want to publish it now. THIS IS GREAT NEWS.
I will come back and update the text. Also with references.

7 kommentarer:

  1. There are defiantly some great benefits to fasting. Since I have changed my diet I have lost some pounds and feel great. The key like you mention is finding one that is easy to follow. I recommend the Renegade Diet http://fastingreviews.com/the-renegade-diet-review/

  2. This was more about intermittent fasting, but there are health benefits also in the low-calorie diet, still unsolved. The eating question is very difficult and complex.

  3. Eating Fat Makes Mice Brain Want More


  4. http://matpitka.blogspot.com/2012/05/it-is-interesting-to-try-to-develop.html






  5. Researchers at NYU School of Medicine have, for the first time, identified a single gene that simultaneously controls inflammation, accelerated aging and cancer. http://communications.med.nyu.edu/media-relations/news/key-gene-found-responsible-chronic-inflammation-accelerated-aging-and-cancer

    “This was certainly an unexpected finding,” said principal investigator Robert J. Schneider, PhD, the Albert Sabin Professor of Molecular Pathogenesis, associate director for translational research and co-director of the Breast Cancer Program at NYU Langone Medical Center. “It is rather uncommon for one gene to have two very different and very significant functions that tie together control of aging and inflammation. The two, if not regulated properly, can eventually lead to cancer development. It’s an exciting scientific find.”

    Molecular Cell - mRNA Decay Factor AUF1 Maintains Normal Aging, Telomere Maintenance, and Suppression of Senescence by Activation of Telomerase Transcription, http://www.sciencedirect.com/science/article/pii/S1097276512003413

    For decades, the scientific community has known that inflammation, accelerated aging and cancer are somehow intertwined, but the connection between them has remained largely a mystery, Dr. Schneider said. What was known, due in part to past studies by Schneider and his team, was that a gene called AUF1 controls inflammation by turning off the inflammatory response to stop the onset of septic shock. But this finding, while significant, did not explain a connection to accelerated aging and cancer.

    When the researchers deleted the AUF1 gene, accelerated aging occurred, so they continued to focus their research efforts on the gene. Now, more than a decade in the making, the mystery surrounding the connection between inflammation, advanced aging and cancer is finally being unraveled.

    The current study reveals that AUF1, a family of four related genes, not only controls the inflammatory response, but also maintains the integrity of chromosomes by activating the enzyme telomerase to repair the ends of chromosomes, thereby simultaneously reducing inflammation, preventing rapid aging and the development of cancer, Dr. Schneider explained.

    Inflammation is associated with DNA damage, cellular senescence, and aging. Cessation of the inflammatory cytokine response is mediated in part through cytokine mRNA degradation facilitated by RNA-binding proteins, including AUF1. We report a major function of AUF1—it activates telomerase expression, suppresses cellular senescence, and maintains normal aging. AUF1-deficient mice undergo striking telomere erosion, markedly increased DNA damage responses at telomere ends, pronounced cellular senescence, and rapid premature aging that increases with successive generations, which can be rescued in AUF1 knockout mice and their cultured cells by resupplying AUF1 expression. AUF1 binds and strongly activates the transcription promoter for telomerase catalytic subunit Tert. In addition to directing inflammatory cytokine mRNA decay, AUF1 destabilizes cell-cycle checkpoint mRNAs, preventing cellular senescence. Thus, a single gene, AUF1, links maintenance of telomere length and normal aging to attenuation of inflammatory cytokine expression and inhibition of cellular senescence.

    “AUF1 is a medical and scientific trinity,” Dr. Schneider said. “Nature has designed a way to simultaneously turn off harmful inflammation and repair our chromosomes, thereby suppressing aging at the cellular level and in the whole animal.”

    With this new information, Dr. Schneider and colleagues are examining human populations for specific types of genetic alterations in the AUF1 gene that are associated with the co-development of certain immune diseases, increased rates of aging and higher cancer incidence in individuals to determine exactly how the alterations manifest and present themselves clinically.

    After http://nextbigfuture.com/2012/05/key-gene-found-responsible-for-chronic.html

  6. http://www.sciencedaily.com/releases/2013/08/130815161545.htm

    DNA binding proteins called transcription factors are required for maintaining cell identity. They ensure that daughter cells have the same function as their mother cell. However, each time a cell divides the specific binding pattern of the transcription factors is erased and has to be restored in both mother and daughter cells. Previously it was unknown how this process works, but now scientists have discovered the importance of particular protein rings encircling the DNA and how these function as the cell's memory.

  7. http://www.scribd.com/doc/57754705/Presman-Electromagnetic-Fields-and-Life-1970#scribd