title bar
                             home   news   views   family   info  
previous Health items

Health Items from 2012:                                                  to enlarge a photo, click on it

Why placebos work    Handedness and disease    Dyslexia 7    Metabolic Syndrome    The fights about the DSM-5    Bits about nutrition    Why is stress bad for us    Autism debates   Notes on epigenetics and similar   Myths about eating disorders     The polio affair   Cost of erect posture    Maybe good news   Misfolded protein diseases     Computerized health   The obesity paradox   Antibacterial soaps   New med for my joints    Genetics textbooks will have to be rewritten    Dealing with stress    Why is there a flu season?     Biological energy 

Why placebos work
Placebos work but why? Here is a cut down version of what Nicholas Humphrey says in Edge:

“Now, when people are cured by placebo medicine, they are in reality curing themselves. But why should this have become an available option late in human evolution, when it wasn't in the past.
I realized it must be the result of a trick that has been played by human culture. The trick is to persaude sick people that they have a 'license' to get better, because they're in the hands of supposed specialists who know what's best for them and can offer practical help and reinforcements. And the reason this works is that it reassures people – subconsciously – that the costs of self-cure will be affordable and that it's safe to let down their guard. …
To explain placebos I think we need to invoke the existence of an 'evolved health management system'. The placebo effect is a particular kind of priming effect...If people have the capacity to heal themselves by their own efforts, why not get on with it as soon as needed? Why wait for permission – from a sugar pill, a witch doctor – that it's time to get better?
Presumably the explanation must be that self-cure has costs as well as benefits. What kind of costs are these? Well, actually they're fairly obvious. Many of the illnesses we experience, like pain, fever and so on, are actually defenses which are designed to stop us from getting into more trouble than we're already in. So 'curing' ourselves of these defenses can indeed cost us down the line. Pain reduces our mobility, for example, and stops us from harming ourselves further; so, relieving ourselves of pain is actually quite risky. Fever helps kill bacterial parasites by raising body temperature to a level they can't tolerate; so again, curing ourselves of fever is risky. Vomiting gets rid of toxins; so suppressing vomiting is risky.
The same goes for the deployment of the immune system. Mounting an immune response is energetically expensive. Our metabolic rate rises 15 percent or so, even if we're just responding to a common cold. …
Given these costs, it becomes clear that immediate self-cure from an current illness is not always a wise thing to do. … In general it will be wise to err on the side of caution, to play safe, not to let down our defenses such as pain or fever until we see signs that the danger has passed”



Handedness and disease
So the old myths about the diseases of left-handers are mostly wrong. They do not have more accidents and do not die younger. But there are links with dyslexia, schizophrenia and attention deficit hyperactivity disorder. Some believe that these links are not just true of lefties but also extreme righties.
Being left-handed is only partially genetic and also depends in some not understood way on how a baby's brain develops in the womb, possibly the effects of stress/cortisol in the mother.
There is no difference in intelligence that correlates with handedness. Lefties do better on a form of creativity called divergent thinking. They earn less than righties by about 10% but are often leaders (half of last 12 US presidents were left-handed compared to a tenth of the population). They are better at some sports but only interactive ones because they are more familiar with playing against rightie than the righties are with playing against lefties.
Typically in right-handers, the brain's left side is dominant. But this tendency doesn't hold up with lefties, as scientists previously believed. Some 70% of lefties rely on the left hemisphere for their language centers, a key brain function. This doesn't appear to present problems. The other 30% of lefties appear to exhibit either a right-dominant or distributed pattern. They may be more prone to impaired learning or functioning, and at greater risk for brain disorders. Ambidextrous people are more prone that left-handed ones to ADHD and it may be the distributed pattern in the 30% of lefties that is problematic.
Because left-handed people differ from the majority and even without their group in how the brain is lateralized, many studies carefully exclude lefties from their subjects. This is one of the reasons that less is known about how lefties' brains work.

Dyslexia 7
The type of dyslexia I have (the one due to poor phonological awareness: poor ability to distinguish, pay attention to and mentally manipulate individual speech sounds ) has more or less been tied down.
The normal situation is that the right auditory cortex is tuned to hear phonemes and the left auditory cortex is better at syllable sized pieces of sound. In other words that is an asymmetry between the two halves of the brain in how they hear. This matches the asymmetry in how language is processed in the two hemispheres.
A syllable takes about a quarter of a second while its component sounds are much shorter maybe averaging around a 10th of a second. These speech sounds must be 'sampled' to follow their ups and downs if they are to be accurately identified. For example a short consonant like 'b' has to be sampled enough to differentiate it from 'p'. Too much sampling is wasteful and too little will not 'hear' the difference in the phonemes. A rhythm called the low-gamma is used to examine the structure of phonemes and a rhythm called delta/theta is used to characterize syllables. The two rhythms nest. The information is discretized at phonemic level and then is integrated at syllabic rate.
In this type of dyslexic, the low-gamma sampling is not there in the left hemisphere auditory area – the two halves of the brain are symmetrical. What this means is that dyslexics hear syllables fine but as wholes (not sequences of shorter sounds). This is why they can learn and understand oral language – they are distinguishing syllables. There are indications of this if they are looked for but none serious enough to interfere with learning oral language.
Written language using phonological letter systems is another thing. If the fine structure of consonants is not perceived than it is difficult to use this level of sound to identify words on the page. The task is to learn to identify phonemes from the syllable level perception. First the young dyslexic has to be let in on the secret – they have to be told about the structure. Then they have to have phonetics practice to learn how to recognize the phonemes from the information they have.
It is possible to get indications before children start to school as to whether they may have problems. They can be tested for abilities to notice rhyming or words starting with the same sound, being able to separate sounds in a word (asked to say 'cowboy' without the 'cow), having picked up on some relationships between letters and sounds by themselves. There are also scanning indications: reduced activity in the junctions between the occipital and temporal lobes and the temporal and parietal lobes in the back of the brain. There is no increased activation of frontal regions in pre-schoolers. This only occurs after the children attempt to learn to read, probably in compensation for the brain areas that are not working properly, they are using frontal areas to compensate.

 

Metabolic Syndrome
Over the years I have become angry with those who simplistically say that people who are fat have only their eating habits to blame. There is even doctors in the UK who feel they can withhold treatments from the obese because it is a life-style problem and until the patient cures their obesity and is worthy the the doctor's attention, any other condition they may have can wait. How ignorant can the well-educated doctor be? My husband cannot remember being hungry – he knew he had been – but can't remember the event as it was so long ago. I cannot remember the last day that I was not hungry for part of the day – just too long ago, about the time I quit smoking. I have stopped dieting and just lose weight slowly so as not to gain. If I lose quickly, I gain it back with interest. Instead of worry about weight, I worry about nutrition and exercise. The theory below was on the Edge website. The Wight family seems to be prone to being overweight, have heart problems and type 2 diabetes, so I cannot assume that I am being poisoned, especially as I have lived since retiring with not much contact with Golomb's list of toxins. I would even disagree with some of her list being toxic, but in general she could be right. Below is Golomb's piece.
The Epidemic of Obesity, Diabetes and “Metabolic Syndrome:” Cell Energy Adaptations in a Toxic World? - Beatrice Golomb Prof of Medicine UCSD
"Metabolic syndrome" (Met Syn) has been termed the "Epidemic of the 21st century." Met Syn is an accretion of symptoms, including high body mass index (weight-for-height), high blood sugar, high blood pressure (BP), high blood triglycerides, high waist circumference (central/visceral fat deposition), and/or reduced HDL cholesterol, the so-called "good" cholesterol. Epidemics of Obesity and diabetes are intertwined with, and accompany, the meteoric rise in Met Syn.
The prevalent view is that Met Syn is due to a glut of food calories ("energy") consumed, and a dearth of exercise energy expended, spurring weight gain an "energy surfeit" with the other features arising in consequence. After all, we have more access to calories, and are more often sedentary, than in times gone by. In turn, Met Syn factors are each linked, in otherwise-healthy young populations, to higher mortality.
But this normative view leaves many questions unanswered: Why do elements of Met Syn correlate? Why are overweight people today more likely to have diabetes than hitherto? Why are elements of Met Syn now emerging in infancy? Why is Met Syn materializing in poor and third-world nations?
The customary "explanation" also creates paradoxes. If Met Syn stems from energy surfeit, why do factors that reduce energy supply, or increase demand promote Met Syn far from protecting against it?
Sleep apnea (It’s a stronger Met Syn risk factor than overweight, though oxygen is the primary energy substrate; moreover sleep apnea treatment benefits each Met Syn element)
Ultra low-calorie or low-fat diets
Fasting, skipped meals
Hypoglycemia-promoting diets (high-carbohydrate/low-fat/low-protein diets lead to unopposed insulin surge)
Deficient sleep (more energy-expending wake time)
Illness/injury/surgery (high energy demand)
Cold weather (mandating energy expenditure for thermo-genesis)
Nutrient and antioxidant deficiencies (adequacy required for energy production)
Oxidative stressor exposure (impairs function of mitochondria, the energy producing elements of cells)
Mitochondrial pathology.
Why do factors that protect from energy-deficit, reduce Met Syn? factors: antioxidant cocoa and cinnamon, mitochondria supportive coenzymeQ10—and exercise, which expends energy during activity, but boosts energy production throughout the day/night, via antioxidant effects, mitochondrial biogenesis, enhanced circulation and cardiopulmonary function improving oxygen intake, delivery, and conversion to energy.
Why does Met Syn cease to elevate mortality (indeed, sometimes boosts survival) when the group studied has advanced age, heart failure, or severe kidney disease conditions that all impair cell energy?
Suppose the correct explanation were the complete opposite to the accepted one? Could the features of Met Syn be the adaptive response to inadequate energy? After all, fat depots, glucose, and triglycerides are each accessory energy sources (oxygen is primary), blood pressure is needed to deliver these to tissues, especially when under-perfused. Cell energy, central to cell and organism survival, is needed continuously (we live only minutes without oxygen). The stretch is not so great: populations in which prior generations were energy starved have increased obesity/Met Syn now ("thrifty gene" thesis); and low energy supply in utero is understood to foster Met Syn in adulthood.
This explains as the energy surfeit view does not why Met Syn exists at all: why elevated glucose, triglycerides, blood pressure (carrying oxygen, glucose, nutrients) and abdominal fat deposition cohere statistically. It explains why other energy supportive adaptations accompany them, like free fatty acids as well as (metabolically active) ectopic fat: fatty-liver, fatty-pancreas, fatty-kidney even fatty-streaks in the blood vessels; why Met Syn is linked to fatigue, and increased sleep duration (to conserve energy). Indeed, increased calories eaten, and reduced exercise expended the usual Met Syn explanation arise, too, as fellow energetic adaptations: Thus, this view is arguably not antithetical to the canonical one, but in one sense subsumes it. It explains, as the energy surfeit view does not, the populations at risk for Met Syn such as elderly (mitochondrial function declines exponentially with age) and those afflicted with sleep apnea or any cause for recurrent energy production impairment. And it explains why in studies focused on persons with conditions that blight energy, those with Met Syn features "paradoxically" don’t do worse, or even fare better.
Why, then, is Met Syn an epidemic? Numerous energy-adverse secular shifts include nutrient-poor/low-antioxidant/high-prooxidant pseudofoods (nutrients are needed for energy production machinery, antioxidants protect from oxidative stress for which the chief target is mitochondria, the energy producing bits of cells), decline of regular balanced meals, hypoglycemic-promoting macronutrient composition (simple carbohydrates without fat or protein engender unopposed insulin surges: glucose drops). But a central factor is the explosion of oxidative stressors in our environment which disrupt function of (and DNA in) mitochondria, cells’ energy-producers, e.g.:
Metals and heavy metals (mercury in fish, high fructose corn syrup, broken light bulbs; arsenic to promote poultry growth; aluminum vaccine adjuvants)
Plastics with bisphenol A
Personal care products (chemicals in sunscreens, lotions, hair dyes, cosmetics, detergents, fabric softeners/dryer sheets, conditioners)
Cleaning products
Furnishings/clothes with formaldehyde (pressboard, no-iron cotton)
Petrochemicals, combustion products
Electromagnetic fields (electronics, cellphones, smart-meters)
Fire retardants (pajamas, bedding)
Dry-cleaning chemicals
Air "fresheners"
Pesticides, herbicides (potent oxidative stressors, now routinely applied at homes, recreational-sites, professional buildings)
Termite tenting
Prescription and OTC drugs including antibiotics with exposure directly and through our food supply
Antimicrobial soaps bearing active ingredients largely unfilterable from the water supply
Air and water pollutants/contaminants
Artificial ingredients in foods transfats, artificial-sweeteners, dyes, preservatives.
The energy deficit ("starving cell") hypothesis accounts for scores of facts where the prevailing view provides no insight. Numerous observations deemed "paradoxical" in the standard view emerge seamlessly. It has testable predictions, e.g.: Multiple other oxidative stress and mitochondrial disruption inducing exposures that have not yet been assessed will promote one or multiple elements of Met Syn. For factors that relate at both extremes to Met Syn e.g. short and long sleep duration the energy disruptive one will prove to cause Met Syn, and the energy supportive one to serve as a fellow adaptive consequence.
This reframing addresses a pivotally important problem some think Met Syn is slated to reverse the gains we have made in longevity with a perhaps surprising conclusion, that should precipitate a revision in our thinking about causes of Met Syn, and importantly, its solutions.


The fights about the DSM-5
The American Psychiatric Association publication 'Diagnositic and Statistical Manual of Mental Disorders' is currently nearing the end of being rewritten to produce the fifth edition. This is the psychiatric bible and very important for record keeping, medical stats, treatments available, insurance claims, legal cases, charity status and many other areas. And there are lots of complaints.
  1. At the start, the task force had to sign nondisclosure agreements, unlike the writers of previous editions. Transparency is important if the manual is to be accepted by the profession – they will want to be able to challenge or advise before criteria are written in stone for another decade. The agreements were relaxed in the face of criticism but the process is still not as transparent as many would like.
  2. Many members of the task force have ties to industry – more than in previous updates. There is worry about the effect of these members. Are conditions being created because there is a drug for it? There are no safeguards.
  3. There are complaints about methodology (or lack of it).
  4. Two particular members of the task force have had petitions circulated to remove them because they are not considered suitable. Phrases like 'junk science' and 'hurtful theories' have been used.
  5. There are people who believe that the manual is culturally blind. It is too short-sightedly American.
  6. There are complaints that the manual continues the tendency to make diseases out of natural responses to life and to make illness out of normal variation.
  7. Some of the specific changes are disliked. For example, normal grief is going to be considered a episode of major depression; it will be labelled in a person's medical record and they will have medication and/or therapy for it. The changes to the diagnosis of autism to include Asperger's but to tighten the criteria has caused a lot of problems. There are children now supported that would lose their support. Children who have not had the stigma of 'autism' that will now have it. Very many parents and their organizations are hopping mad. They are accused of trying to make chronic fatigue syndrome/myalgic encephalomyelitis into a pyschological disease rather than a normal medical-type disease just by putting it in the manual without any proof that it may be a mental disorder.
The process of writing this manual has a year to go, so it may turn into a silk purse before the end – don't hold your breath. The task force is already attacking its critics – even suing some.


Bits about nutrition
In general I am not very trusting of nutritional information in the popular press. Anyone can call themselves a nutritionist and spout any kind of rot and someone will publish it. That is why when I run across a report that appears trustworthy and not widely known, I have been filing a copy. I am getting too many files of various kinds and so I have been clear out old files from my computer and I find that I have many reports filed under nutrition. I am tossing most of them but only after making a note or two on each. This is long, not well organized and I apologize, but I had not done it originally to be in my webpage. Here is some of these notes, which you may find interesting:
Apple peels – Screening 1300+ compounds to find treatment for muscle atrophy (loss the muscle mass in aging, fasting, forced inactivity) – only 1 compound found effective, ursolic acid, found in high amounts in apple peal – also somewhat effective at lowering cholesterol and blood sugar, losing fat, increasing strength - ursolic acid useful for muscle atrophy, obesity, metabolic syndrome, type 2 diabetes, slowing cancer growth and inhibiting Alzheimer proteins - has a effect on the expression of some genes – apple skin polyphenols in mice protected from colitis – inhibition of T cells gives protection from autoimmune gut diseases: inflammatory bowel, ulcerative colitis, Crohns, colorectal cancer. First author on papers: Kunkel, Shishodia, Pathak, Wilkinson, Skyberg
Calcium supplements – dietary intake of 750 mg a day is good and there is no advantage to more Ca for aging women – very high intake may increase the risk of fractures – taking Ca supplements without Vitamin D is useless – Ca supplements increase risk of heart attacks and stroke in older women (1000 older women on 500mg Ca supplements and no Vitamin D supplements for 5 years will prevent 26 bone fractures and cause 14 heart attacks, 10 strokes and 13 deaths) – high blood calcium linked to harden of arteries - eating soy, dairy, fruits, veg, legumes, fish gives adequate Ca and does not increase risk to heart – use diet and Vit D rather than Ca supplements – obtaining Ca from diary products and taking Vitamin D supplements assisted in weight lose with several types of dieting. First author on papers: Warensjo, Bolland, Bostick, Hsia, Ross, Shah, Wang, Reid, Shadar
Chocolate – chocolate is a richer source of antioxidants, polyphenols and flavanols than fruit juice – but 'super fruit' content is not found in chocolate processed by alkalization (hot chocolate) – dark chocolate protective against heart disease – catechins and procyanidines in cocoa related to those in green tea and inhibit the enzyme ACE lowering blood pressure – lowering of ACE comparable to ACE inhibiting drugs. The flavonoid epicatechin found in dark chocolate (and epicatechin-enriched cocoa) heals mitochrondria damaged by diabetes and heart disease. The damaged mitochrondria cause the lack of energy, shortness of breath and difficulty walking in these conditions. Epicatechin increased the size, number and abundance of internal cristae in muscle mitochrondria. First author on papers: Crozier, Persson, Taub
Baker's yeast – beta-glucans promotes healing, fight infection, inhibit cancer growth – enhances the innate immune system – being tested against allergies, asthma, chronic fatigue syndrome and cancer, all disorders related to innate immune system – commercial product used in vet practice. First author on papers: Jakobsen
Citrus fruit – Vitamin C and flavonoids both reduce stroke risk – 6 types of flavonoids compared (flavanones, anthocyanins, flavan-3-ols, flavonoid polymers, flavonols, flavones) for risk of ischemic, hemorrhagic and total stroke – women eating high flavanones in citrus had 20% reduction of ischemic (clot) stroke – in another study citrus but not many other fruits protected against ischemic stroke and intracerebral hemorrhage, exceptions were apples and pears – flavanone especially lowers stroke risk – tangerines contain the flavonoid, nobiletin, which protects against obesity, type 2 diabetes and atherosclerosis, metabolic syndrome. First author on papers: Rimm, Mulvihill
Red wine – Resveratrol is in red but not white wine and found in dark grapes – resveratrol is not very stable – many different polyphenols made from it – resveratrol stimulates the hormone adepoectin made by fat cells – both resveratrol and adiponectin have anti-obesity, anti-insulin resistance and anti-aging properties – resveratrol like rapamycin inhibits mTOR – resveratrol shown to be anti-aging, anti-carcinogenic, anti-inflammatory, antioxidant – plants seem to produce it as a defense against microorganisms – reduces cardiovascular diseases – believed by some to account for the anomaly in French diet of high saturated fat with low cardiovascular disease – reveratrol reduces the accumulation of triglycerides – red wine drinking has J shaped curve increased consummation giving lower disease to a point and then further increase has a bad effect, optimum 1-2 glasses per day – best source of reveratrol is the skins, seeds, stems of grapes – foremost benefit of red wine is lowered risk of cardiovascular disease but also lowers risk of some types of cancer, stroke, type 2 diabetes, macular degeneration, Alzheimers, vascular dementia, kidney and gallstones, bone loss, fractures – Polyphenols from grape seed reduced the accumulation of Abeta56 neurotoxin in mice and so will be tested in Alzheimers – resveratrol mechanism does not involve sirtuin as once thought (sirtuin lenghtens life in calorie restriction) – resveratrol targets and reduces PDE4 in skeletal muscle and this indirectly activates sirtuin1 – it targets other proteins besides PDE4 with effects that have not been studied. Resveratrol can counteract some effect of lack of activity and weightlessness – it inhibits a inflammation switch NF-kB. First author on papers: Wang, Smoliga, Lasa, Ayala, Liu, Park, Momken, Buhrmann
Vitamin D - many (maybe most) people are deficient in Vit D – gum cells treated with Vit D produce endogenous antibiotic protective of gingivitis and periodontitis – white cells and lung cells also produce antibiotic activity and that increases with Vit D – Vit D coordinate the expression of a number of genes not previously considered part of Vit D pathways – protects against infections, autoimmune disease and some cancers – there is controversy about Vit D studies: epidemiological studies show benefits (huge numbers of subjects but not random) from Vit D supplements and clinical trials do not (standard random clinical trails with small numbers) – the controversy is around cardiovascular protection and the exact minimum level for Vit D – Vit D deficiency found in people far from the equator, elderly, adolescent, darker skinned, with conditions (obesity, diabetes, liver disease, celiac, renal disease) – every tissue has Vit D receptors and needs it for functioning – assists in absorption and regulation of Ca for bone, teeth and muscle – activates genes the regulate immunity and brain function – thought to be involved in SAD depression – Vit D used by some doctor treating depression – Vit D has been shown to reduce inflammation – clear chain of cellular events from DNA binding to reduction of proteins involved in inflammation – Vit D needs to be adequate for those with asthma, cancer, diabetes, arthritis and other chronic inflammatory diseases – lack of Vit D increases the aggressiveness of colon cancer by interfering with beta-catenin – we can get Vit D from fish oil, milk if fortified and exposure to sunlight. The fish salmon, mackerel, sardines and egg yolks are rich in Vit D. Diet gives Vit D2 and sunlight D3. Confusion in normal levels etc. may have resulted from blood tests that measured only one type. Vit D injections are now routine in UK for patients with low levels. First author on papers: Diamond, Jassal, Greenblatt, Zhang, Larriba, Shah
Foods containing luteolin (carrots, peppers, celery, olive oil, peppermint, rosemary, chamomile) – luteolin reduces age-related inflammation of the brain and inhibites memory deficits - microglial cells trigger cytokine cascades in the brain (inflammation) which causes sleepiness, loss of appetite, memory deficits and depression - during aging microglial cells become dysregulated and produce excessive levels of inflammation - luteolin inhibits inflammation in the brain as well as elsewhere in the body. First author on papers: Jang
Chrondroitin sulfate supplements – controlled random tests show that patients with osteoarthritis have less pain, improved strength and less morning stiffness using chrondroitin supplements of 800 mg/day - alternative pain relief for OA through non-steroidal anti-infammatory drugs (NSAIDs) has more toxic side-effects. First author on papers: Gabay
Coriander oil – used in cooking and also in herbal medicine coriander is used against pain, cramps, convulsions, nausea, indigestion, fungal infections - tests have been made on the effect of coriander oil on a range of disease causing bacteria and it was found to slow the growth of all and kill most - the mechanism was found to be damages to the bacterial cell wall. First author on papers: Sliva
Garlic – used in folk medicine, food preservation and cooking - antimicrobial activity was thought to be due to garlic's phenolic compounds and volatile thiosulinates, they are effective, but the garlic organosulfur compounds, diallyl sulfides, are even more effective. First author on papers: Lu
Cumin – used in traditional medicine to treat many conditions: vitiligo, hyperglycemia, parasites, bacterial infections, fever, pain - tests have shown it can reduce fever and be a painkiller - recent tests have found high levels of antioxidants (involved in atherosclerosis, neural degenerative disease, inflammation, cancer and aging) - it is rich in phenolic antioxidants. First author on papers: Ani
Turmeric (curcumin) – thought to lower chances of cancer and Alzheimers – it is a potent anti-inflammatory and antioxident. It has been shown to reduce the size of a hemorrhagic stroke - patients with bleeding in the brain can be treated for headache and nausea but the clot has to be removed with surgery. It was found that curcumin decrease the size of a blood clot in the brain. In a study to find treatments for ischemic stroke and traumatic brain injury, CNB-001 dervived from curcumin was highly neuroprotective. It also enhanced memory. It maintains specific cell signaling pathways required for nerve cell survival. Colorectal tumours can leave chemo-resistant cells causing future recurrents of the cancer. Curcumin can increase the effectiveness of chemotherapy. There are current investigations into using curcumin for Alzheimers and arthritis – especially turmeric but also other antioxidant spices especially in combination (rosemary, oregano, cinnamon, turneric, black pepper, cloves, garlic, paprika) decrease the negative effects of red meat (high blood fat). Two tablespoons of spice in a meal is equivalent to 5 ounces of red wine or 1.4 ounces of dark chocolate in their healthy effect on blood fat and insulin response – tumeric can be used to treat tendinitis and some forms of arthritis by inhibiting the inflammatory switch NF-kB. First author on papers: McCracken, Gomez-Pinilla, Lapchak, Brown, Skulas-Ray, Buhrmann
High water intake – there is no good evidence for the 6-8 glasses of water a day and it can be harmful to a few. Avoiding any thirst is enough fluid for most. First author on papers: McCartney
Green tea – green tea has powerful ability to increase regulatory T cells which improves immunity, suppresses autoimmune disease with low toxicity compared to other similar drugs. The active compound is a polyphenol, EGCG, which has an epigenetic mechanism. Epigenetic regulation can be used to generate suppressive regulatory T cells for suppression autoimmune diseases. First author on papers: Wong
Iodine – goiter (lower thyroid hormones) disappeared when iodine was added to salt but is returning. We use less salt at home and more in commercially prepared food which uses salt without iodine. Iodine was used in processing flour and bromide has replaced it. Bromide replaces a quarter of the iodine intake and also blocks iodine activity in the body. So does the chlorine and fluoride in water. Potassium bromate is a class 2B carcinogen. The result of all this is a 50% drop in iodine intakes. It is impossible to achieve optimal general health without adequate iodine. Iodine deficiency increases risk of breast cancer. It may be involved in CFS and fibromyalgia, also weight gain, low body temperature. To increase iodine in the diet: obtain iodized salt, eat seafood and seaweed, avoid unfermented soy products. First author on papers: Teitelbaum
Walnuts (and other nuts) – all nuts are good but walnuts have twice as much and better quality antioxidants than any other nut – nuts have high-quality protein which can substitute for meat, vitamins/minerals, dietary fiber and they can be eaten in vegetarian diets and also dairy and gluten free diets. Studies have shown that they decrease risk of heart disease, some kinds of cancer, gallstones, type2 diabetes – walnuts are usually raw rather than roasted which protects its antioxidants. All the nuts contain polyunsaturated and monounsaturated fats – omega-3 fatty acids like alpha linolenic acid in walnuts, walnut oil and flax seed reduce LDL (bad) cholesterol, c-reactive protein and inflammation, low blood pressure (especially diastolic) and blunt cardiovascular responses to stress. Eating nuts daily as replacement for some carbohydrates can help type2 diabetics to control blood sugar and lipids - nuts can reduce HbA1c by two-thirds – nut consumption not associated with weight gain - First author on papers: Vinson, West, Jenkins
Broccoli and Cruciferous vegetables – to get the healthy compounds the cabbage family you cannot use supplements but can only eat the whole foods and only raw or lightly cooked. Glucosinolates, the valuable chemicals, are difficult to absorb without an enzyme called myrosinase. The enzyme is missing from supplements and over cooked veg. It breaks the glucosinolates into sulforaphane and erucin. They are believed to reduce risk of many cancers by suppressing cancer growth and detoxifying some carcinogens. There is more glucosinolates in broccoli but they are also in cauliflower, cabbage, kale etc. along with myrosinase. The chemical in broccoli etc. that selectively kill cancer cells while leaving normal prostate cells unaffected is sulforaphane - it is under trail now for prostate and breast cancer treatment – it inhibits histone deacetylase (HDAC) – HDAC affects whether some genes are expressed or not – this is an epigenetic mechanism – also sulforaphane acts in a second epigenetic way, DNA methylation – The two working together may maintain proper cell function. First author on papers: Clarke
Omega 3 – Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are common in fish - low blood levels of omega-3 fatty acids are correlated with lower brain volumes as in aging (equivalent to about 2 years extra aging in the elderly) – omega-3 in fish oil (or flax oil but need more) can reduce the signs and symptoms of osteoarthritis – modern diet is up to 30 times out in the best ratio of omega-6 to omega-3 - omega-3 has a protective effect on cardiac health - healthy neuro function depends on omega-3 - DHA deficiency reduces cognitive ability and affects emotional/mode/behaviour and causes depression - the endocannabinoid system ( involved with learning and mood) uses lipids for signaling and require omega-3 for proper functioning. First author on papers: Tan, Tarlton, Lafourcade
Fructose – fructose intake as sucrose and high fructose corn syrup is very strongly linked to obesity, nonalcoholic fatty liver disease, metabolic syndrome and type 2 diabetes. It causes visceral organ fat accumulation and insulin resistance. This is not the effect of the calories but of the fructose. Sensitivity to the effects vary between individuals and this is because there are two pathways for metabolizing fructose, one dangerous and one protective – the opposing effects of fructokinase C and A isoforms. First author on papers – Ishimoto
Best and worst for weight loss – 20 year study of 120000 people – food associated with most weight gain in order: potato chips, French fries, sugar-sweetened beverages, unprocessed red meat, processed meats, sweets and desserts, refined grains – food associated with most weight loss in order: yogurt, nuts, fruits, whole grain, vegetables – the key is satisfaction due to higher fiber content and slower digestion – another study used 2 diets, one higher in fats and lower in carbohydrates, one higher in carbohydrates and lower in fats, same calories, neither gave significant gain or loss – but higher fat and lower carbs gave reduction in abdominal fat – when total calories reduced in both diets to cause weight loss, there was more loss on the higher fat lower carb diet. First author on papers: Mozaffarian, Gower,
Potato – potato has a bad reputation but it is not all bad – fried potato is bad because frying temperatures change the chemicals in potato as well as adding usually saturated fat – unpeeled potatoes, microwaved, eaten without additions are very healthy – they lower blood pressure even in those taking anti-hypertension meds – contains ACE inhibitor and some of the chemicals in broccoli, spinach and other vegatables. First authors on papers: Vinson
Chicken thighs – poultry dark meat and some sea food contains taurine – it lowers risk of coronary heart disease in women with high cholesterol (but not with normal chol). It has not been tested on men or non-Caucasians. First author on papers: Oktawia
Vitamin E – the mechanism of Vit E has been a mystery until recently – it is an antioxidant that repairs tears in the plasma membranes of cells – it is lipid soluble in sits within the membrane – high glucose and strenuous exercise can impede membrane repair and Vit E counteract them – it is found in a great many foods. First author on papers: Howard
Vitamin C – nerve cells in the retina require a lot of Vit C – this is probably true of neurons in the brain - GABA-type receptors need Vit C to function – in Vit C deficiency, the brain's supply seems to be protected at the expense of the body's – a symptom of scurvy is depression. First authors on papers: Cho
Tomato – tomatoes contain 9-oxo-octadecadienoic acid which has anti-dyslipidemic affects (controls abnormal amounts of cholesterol and fat in the blood) and so are protective against vascular diseases (arteriosclerosis, cirrhosis) – the compounds enhances fatty acid oxidation and assists the liver in regulating lipid metabolism – tomatoes contain many other beneficial compounds. First authors on papers: Kim
Supplements - consuming dietary supplements, including multivitamins, folic acid, iron and copper, among others, appears to be associated with an increased risk of death in study of 38000 older women with most dangerous: multivitamins, vit B6, folic acid, iron, magnesium, zinc and copper – Danish study found Vit E, VitA, beta-carotene supplements harmful – supplements should be used to reduce actual deficiency and not to promote wellness in healthy individuals showing no deficiency – more is not better – Vit D and calcium were not found to be dangerous in these two studies. First authors on papers: Robien, Bjelakovic

Why stress is bad for us
It has been unknown for some time that stress is bad for the health. Prolonged psychological stress is associated with depression, heart disease, infections, asthma and autoimmune diseases (rheumatoid arthritis, Type 2 diabetes, metabolic syndrome, atherosclerosis and other chronic inflammatory conditions). But how this happens has been a bit of a mystery.
Sheldon Cohen has found that chronic psychological stress is associated with the body losing its ability to regulate the inflammatory response. "Inflammation is partly regulated by the hormone cortisol and when cortisol is not allowed to serve this function, inflammation can get out of control." Prolonged stress alters the effectiveness of cortisol to regulate the inflammatory response because it decreases tissue sensitivity to the hormone. Specifically, immune cells become insensitive to cortisol's regulatory effect. In turn, runaway inflammation is thought to promote the development and progression of many diseases. The response to viruses include inflammation and when this is magnified by lack of cortisol control, the symptoms are magnified.

Autism debates
Let me be clear on where I stand on the various debates: There is overwhelming evidence that autism is the result of errors in the fetal development of the brain. It has both genetic and environmental causes but these operate before birth and during very early childhood. Further there is no cure but there are treatments that will help the sufferer cope. It is not caused by vaccines. It is not caused by demon possession. It is not caused by bad mothers.
There is no psychological root cause to unearth with psychoanalysis. It is a developmental disease like club foot, hare lip or webbed toes, only much more debilitating and hidden from view until the child is a couple of years old. Plain and simply, the brain does not grow and organize itself properly when it is being created in the embryo.
There is not much that can be done about the genetic risk but there is things that can be done about the environmental risks. There are suspects (heavy metals, pesticides) and they should be investigated and the dangerous avoided. There is also much that can be done to educate and support those with autism and to encourage ways for them to led fulfilling lives. We can stop blaming parents. We can stop endangering children in general by not immunizing them. We can stop the frequent bullying.

Notes on epigenetics and similar
dogmaGenetics used to be simple. There was the central dogma of molecular biology which encapsulated the idea - the genetic code was transcribed from DNA to RNA, and then the RNA was translated into protein, which did the metabolic work of the cell. This flow of information did not run backwards. This is what the process looked like in bacteria. Here is an illustration of this simple process of the central dogma. There is feedback control of the transcription of RNA that depends on the resulting protein being needed or not needed by the cell at that time.
But in non-bacteria (eukaryotes), the DNA is within a nucleus, packaged to form chromatin and there are many more processes going on in the nucleus in isolation from the rest of the cell. The old dogma may still be the general idea but there is now a lot of elaboration of the role of RNA and even information flowing backwards. The control mechanisms are much more elaborate.
The old nature-nurture debate has become even more meaningless. Some of the new mechanisms come under the heading of epigenetics. (Definition: epigenetics is the study of  heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence.) I have been reading about this new genetics for a while and have collected a lot of files. Now in an effort to cut down on my hard disk use, I am throwing out a lot of this material. But first I am re-reading it and making a few notes.
If you don't have time to read all this – the take home message is that environment and genetics are in constant communication, the whole thing is really, really, really complex, it is weird, and it is not yet well understood.
As blogger EE Giorgi said “The genome is a plastic thing. Yes, that's right: the genome is plastic. No, it's not true that an individual's DNA doesn't change. It's not true that genes dictate what we are, and it's not true that DNA is just a set of instructions. And that we can "build" an organism by simply giving a string of As, Gs, Ts, and Cs. NO!”
General
Plant genetics is more complex and less understood than animal and so I am avoided it here.
stemAll the cells in the body start with the same DNA but the cells of different tissues are very different in the proteins they make. This is because different genes are available for transcription in the different cell lines – liver cells do not need exactly the same proteins as bone cells. What genes are used to make protein, are controlled by the packaging of the DNA and by the ways it is tagged. A human cell has about 2,5 meters (6 ft) of DNA. This is wrapped around protein 'spools', called histone complexes to form something like a string of beads. This is then folded and then further packaged. Very little DNA is showing; most has to have its packaging disturbed in order to be transcribed. There is an illustration of the general idea of the packaging a few headings down.
Also the individual letters in the DNA message can be chemically altered, usually by methylation, so that transcription is not possible. Epigenetics is about methylation, DNA packaging and other ways to affect the use of DNA without any change to the protein specifying information (not mutations in other words).
The first cells in an embryo are stem cells that can become any type of cell and there are stem cells that are more restricted (say can only become types of blood cells). The stem cells undergo epigenetic changes that are almost never reversible and that cuts down the options that they can follow by cutting down on the proteins they can make. They become full developed cell types by this process (muscle for example). Both histone modifications and methylation contribute to these changes. Getting stem cells from fully developed cells is a goal of medicine. It seems to involve changing and/or removing epigenetic blocking of genes.
Epigenetics may be involved in a form of short term change to accommodate an environmental change. Sometimes these can be passed on to future generations but they usually seem to decay in time if they are no longer useful. Many epigenetic effects block either maternal or paternal genes. This allows mothers and fathers to separately effect the genes their offspring can use.
Once transcribed the resulting RNA can be modified or destroyed before being used to create proteins. There are many sorts of RNA translated from DNA and RNA is used for many functions besides translation to protein. Only 2% of human DNA seems to be specifications for protein; 98% is being translated into RNA for other purposes or is not being translated at all. The way RNA functions can also be affected by the environment.
This is the general picture of epigenetics which has been growing for 30 years or so. - various sources
Below are some interesting examples of epigenetics.
Control of speed
Proteins are strings of amino acids which are coded in DNA by codons which are 3 base letters long – giving 64 possible amino acids but the cells use only 20 or so. Some codons are redundant because more than one can code for the same amino acids. The news (a new layer of genetics) is that the redundant codons are not equal. Some pause the production of a protein so that the speed with which a protein is made depends on the number of pausing codons. The final protein is identical. – first author on paper Gene-Wei Li
Grandmother effect
A gene (PHLDA2), a growth suppressor, has a variant RS1 which gives higher baby birthweights, and a variant RS2 gives lower weights. RS2 is found only in humans (about 87% of babies) and seems to have evolved to produce a smaller baby in order to enhance the mother's survival in childbirth. The gene that is inherited from the father is silenced and only the mother's copy is active. If RS1 (big baby variety) is inherited from the mother the baby is 93g bigger on average but if inherited successively from the mother's mother, than 155g bigger on average. - first author on paper Gudrun Moore
DNA clock
Segmented animals (worms, insects, vertebrates etc.) all use a set of genes called HOX genes to lay out the basic plan of the embryo which will then further develop into the young animal. This has to be done in a precise way or things are in the wrong place (a rib out of the neck maybe). Over 48 hours, a segment is built every hour and a half, in order, from head to tail. The genes become active with perfect timing. How? The HOX genes are in sequencial order on the DNA strand and are packaged to make them inactive. The packaging starst to unwind and as each gene is freed, it becomes active. It takes two days to completely unwinding. The DNA, in effect, has a mechanical clock. - first author on paper D. Noordermeer
Identical Twins
Identical Twins have the same DNA but may differ in epigenetic imprinting. Autism spectrum disorders, schizophrenia, bipolar disorder, epilepsy and type 1 diabetes can occur in one identical twin only and this difference may be due to variable epigenetic methylation patterns. - first author on papers  Coolen, Dempster
Mother's diet
Twins and babies of mothers who diet in early pregnancy may have increased risk of obesity and type 2 diabetes during their lives. The research was done on sheep not humans – but effect has been seen in human populations. Genes controlling food intake and glucose levels had epigenetic changes to their histones (DNA packaging proteins) due to the mother's eating habits. The babies are born prepared for the feast or the famine their mothers experienced. - first author on paper Bebgum
Fertilized egg to embryo
Right after fertilization the majority of epigenetic marks on the DNA from sperm and egg are erased (nuclear reprogramming). But some epigenetic marks on particular genes are preserved. Genes are 'imprinted' by the parent of origin. If these processes go wrong the embryo will not survive. TRIM28 is a protein needed for nuclear reprogramming and imprinting. Lack of TRIM28 protein in the egg causes infertility by causing faulty reprogramming and imprinting. - first author on paper Messerschmidt
DNA is usually wound around histones, but in sperm cells most of the DNA is bound by another kind of protein (protamines) and only a small percentage remain with histones. It may be that this is a way for some epigenetic markers to escape destruction in the fertilized egg. A type of rectal cancer may be inherited with an by faulty imprinting. First name on paper - Migicovsky
Three-dimensional DNA
Chromatin Unlike naked DNA rings of bacteria, our 2.5meters (6ft) of DNA is organized in nucleosomes. Each nucleosome (there are roughly 30 million per cell) consists of a 147 base pair segment of DNA. This length of DNA thread is wound 1.67 times around the spool-like protein units, known as histones. The histone complex, together with its windings of DNA, forms the nucleosome core particle. There are complex ways in which the nucleosome partially unwind and allow contact with protein to bind to the DNA. First author on paper - Tims
We have DNA with a complex folding pattern giving it a 3D nature. This puts parts of the DNA that are distant on the string of DNA next to each other by folding. Topological domains (about a million base pairs) are the basic units of folding and have a control function that is not yet clear. - first author on paper Dixon
The genes controlling digits (fingers, toes) are specially folded (this folding is in the cells where the digits are being developed but not in cells elsewhere). Seven enhancers which are located in different parts of the DNA string come into contact through the folding. Various proteins bind to the enhancer locations and interact with one another. The activity of the genes is stimulated and the fingers start to grow. The enhancers appear to be additive. Without each of them the genes work more slowly and the fingers are shorter giving the various genetic malformations of fingers and toes. This mechanism and its variations form all the mammalian digits from hooves to our hands. First author on paper - Montavon
DNA repair
When damaged, DNA can trigger an elaborate alarm system which sets off a chain reaction to slow or terminate cellular processes and wait, while legions of molecules go to work on the damaged DNA.  First author on paper Beli
Influenza
Histone proteins are part of the packaging and transcription control of DNA. The tail of the histone can change the DNA that is hidden in the nucleosome parcel, thus activating or deactivating a gene. Influenza A H3N2 has a protein that resembles the histone H3 tail and uses minic to halt the transcription of genes essential to counteract the infection. First authors on papers – Krasnoselsky, Marazzi
Evolution
Until recently, evolution's mechanism was thought to be only chance mutation of DNA followed by selection of advantageous chances and elimination of disadvantageous ones. A study of evolution of domesticated chicken has added epigenetic changes (methylation) to the mix as a major source of adaptive change. Epigenetic evolution is faster than mutations. It is related to environment conditions rather than random like mutations. Epigenetic changes can also be reversable. In general, it is not known how important epigenetics is to evolution, because in most species there is very limited transfer of epigenetic markers through generations. The evolution of jungle fowl to chickens is mostly epigenetic rather than by mutation. First author on paper – Natt
Toxins
This work was done on rats. Fungicide, pesticides (including DEET and permethrin), plastic, dioxin, jet fuel and some other hydrocarbons can produce epigenetic changes to DNA. A gestating rat's progeny can have affects for multiple generations in ovarian disease (fewer eggs and increased polycystic disease). Ovarian disease has been increasing in the human population (now more than 10%) and this may be a cause. First author on papers – Nilsson, Skinner
Restoring nucleosomes
To synthesize RNA from DNA, the chromosome structure must be loosened to make way for RNA polymerases enzymes. Later, the DNA must be recondensed by the reassembly of the nucleosomes. When the protein Chd1 is not functioning this recondensation is impaired. There is 'histone crosstalk' so that the histones H3 and H2B carry on a complex biochemical conversation. An aggressive type of leukemia in infants seems to have this origin.
Methylation in melanoma
Looking at what it was that UV light did to melanocytes to make them become cancerous, it looks like the difference is in microRNAs (miRs). These are small pieces of transcribed genetic material that regulate the expression of their target genes. Two, miR-375 and miR-34b, were decreased in melanoma cell lines by methylation of their parent DNA. First authors on papers – Mazar, Perera
Cancer pill possibility
Epigenetic switches can cause cancer by switching on oncogenes or swtiching off tumour suppressing genes. There is work on a drug that acts on the enzyme histone deacetylase (HDAC) which normally regulates gene expression by modifying histones. The drug has been licensed for a type of lymphoma even though it has large side-effects. (Side-effects are expected with all epigenetic drugs.) First authors on paper – Udai
Regular cell division is regulated by methylation modifying DNA to ensure cells divide only when needed. In cancer, the methylation process is unbalanced, causing cells to resist regulation and divide uncontrollably. Transforming growth factor beta (TGF-beta) is a hormone that activates the tumor-suppressing gene that stops cell division. ZNF217 gene interferes with this process by binding to the DNA and blocking the tumour-suppressing genes. First author on papers - Thillainadesan
Gene silencing
A protein called Argonaute2 attaches to a piece of 'guide' RNA (the complement to part of the 'target' RNA to be destroyed). The guide and target contact. bind to each other, and then the Argonaute2 enzyme cuts the target so that it can no longer be used to produce its protein product. First author on papers – Schirle
Telomeres and violence
Each chromosome has ends called telomeres that protect the ends from damage. Every time a cell divides, the daughter cells lose some telomere length. This means that cells can divide only a maximum number of times. Smoking, obesity, psychological and physical stress can accelerate telomere losses. Young children who suffer abuse, violence, bullying and physical maltreatment have a dramatic loss of telemere. That is - they are older biologically than their age. First author on paper - Shalev
Transcription factors
There are proteins that control which genes are turned on or off by binding to nearby DNA. As well as 'on' and 'off' there is some sort of dynamic control called 'treadmilling' where there is a high turn over of binding. It gives a quick and responsive adaption of changing environment. First name on papers – Linkwar.
RNA polymerase
The molecular machines that make RNA using DNA templates (translation) are made of a number of subunit proteins. Depending on the choice of subunits, 5 (at least) different RNA polymerases are formed. The II form seems to be involved in RNA-directed DNA methylation and transposon silencing, especially in plants and spermogenesis in mammals. First author on papers - Pikaard
RNA editing in octopuses
Octopuses can range from shallow surface tropical water to deep cold ocean depths. They do a lot of RNA editing (as we all do). The same gene specification can produce differing protein because the intermediate RNA is changed by editing. Octopuses are at the temperature of their surroundings and neurons do not act the same at different temperatures, but octopuses need their large brains. In the range of their temperature there is up to a 60 times difference in the speed of chemical reactions, each reaction changing differently than the others. The cold and warm animals have the same genes but they edit the RNA to regulate the speed of proteins, especially the neural ion channels. Just 8 RNA messengers have been shown to have 100 editing sites available to tune the resulting proteins to it right temperature environment.
Turning on inflammation
When a warning is detected that there is foreign bacteria or viruses in the body, cells change the genes they express to give an inflammatory response. Some areas of DNA are bound by a protein, ARTD1, and it is removed to allow the inflammatory response to start. The way it is removed is that it is cut in two by molecular scissors, the protein caspase7. First author on paper - Erener
Effect of stress
In monkeys, the rank of females is reflected in the genes being used and when the rank changes so do the genes being expressed (within a few weeks). Almost 1000 genes were shown to be expressed in relation to rank. Over 100 were involved in the immune system; this fits with findings that low rank monkeys have compromised immune function. The signal seems to be from glucocorticoid stress hormone system and the mechanism is epigenetic methylation. First author on paper - Tung
Junk DNA
Human DNA is roughly 3 billion letters long. The Human Genome Project was expecting to find millions of genes coding proteins, but only twenty thousand were found. Most of our DNA is not genes! Non-coding DNA is a good name for it but unfortunately it was called junk DNA. It is not junk. Much of the DNA is 'old' genes that have been overtaken by new copies. The 'old' copies remain, are not used and allowed to drift – but it is a resource, a source of building blocks for new genes. Also there is a lot of RNA that has other functions than being translations of active or inactive genes.  There are all sorts of RNA, some with clear epigenetic functions. After the Genome Project there are now projects to inventory all the RNA molecules, an inventory of places where the DNA can be tagged with on-off switches and also an inventory of all the protein molecules. There is a long way to go in understanding the biochemistry of cells.
Types of epigenetic DNA markers
The common type of marker is the addition of a methyl group to a cytosine letter (5mC) but there is a similar mark which adds hydroxymethyl group (5hmC). The 5hmC modification is important in stem cells and fetal development. Marking seems to be different for development, aging and maintenance. First author on paper – Booth
Mapping type 2 diabetes
Some diseases, type 2 diabetes among them, are known to have a large genetic risk factor, but it has been difficult to identify the genes involved. Now it has been shown that type 2 diabetes has a very clear epigenetic signature. Also the telltale methylation locations were shown to appear on the DNA of young individuals who later developed impaired glucose metabolism and then diabetes. First author on papers – Toperoff
RNA inheritance
Double-stranded RNA is not present in healthy cells (only DNA is double-stranded). When a virus introduces dsRNA into a cell, it is sliced into small fragments. The fragments are used by the RNA interference mechanism to identify messenger RNA that matches the fragments and destroy the messages so that they cannot be used to make protein. Thus the viral genes are silenced. This RNA interference can be inherited outside the DNA genome through the inheritance of the small pieces of RNA. First author on paper – Rechavi
Modification of RNA
The FTO gene is associated with obesity and type 2 diabetes. There is a reversible RNA modification which adds a methyl group to a adenosine in the RNA (different from cytocine methylation of DNA). FTO's protein removes the methylation of RNA. Energy equilibrium appears to be regulated using this reversible modification of RNA. First author on papers – Jia
Long non-coding RNA
Much of the 'junk DNA' (not gene – not producing messenger DNA) is transcribed into long RNA molecules that do not code for proteins (lincRNA). Some of these are unique to a particular species of animal while others are highly conserved through evolution. Some human lincRNA molecules can replace similar molecules in zebra fish. They seem to be important in the development of embryos. - First authors on paper – Ulitsky
Thousands of places on mammalian genomes produce long intervening noncoding RNAs (lincRNAs). They are capped, polyadenylated, often spliced RNA molecules greater than 200 letters in length and yet do not encode proteins. Some have been shown to be involved in X chromosome inactivation and in regulation of transcription. Most have not had their function discovered yet. They are often expressed only in specific tissue and at specific times in embryonic development. They are common in central nervous system development. Some lincRNAs in one species resemble messenger RNA in another. This implies that the lincRNA are derived from genes that were duplicated long ago and were copies that lost the ability to encode proteins. This may also mean that some messenger RNA might also function like lincRNA in development.
Prion inheritance
Prions are proteins that are badly folded and can influence well-folded molecules to copy them. One is famous for mad cow disease. If prions are in a cell, they are inherited by daughter cells. Although they are thought of as infectious agents, they may sometimes be beneficial. Many yeasts have been found to have prions and 25 of them are thought to be master switches that control protein translation and RNA transcription. First author on paper – Halfmann
In yeasts, PSI+ is the prion form of the protein Sup35. Sup35 is a factor responsible for the termination of the translation process. When Sup35 is refolded to PSI+ translation can continue through a termination and translational read-through uncovers hidden genetic material. Protein folding is usually mediated by 'chaperone' proteins so that the proteins attain their functional configuration. Chaperones are involved in the response to environmental stresses. Therefore, prion forms of a protein are more likely to occur in stressful situations. Many proteins in many animals have prion-forming parts of their structures. The brain may be a special environment for prions. There is a theory that changes in protein folding (and therefore aggregation) are part of the mechanism of memory. This may be why neurodegenerative diseases are so often associated with build ups of inactive mis-folded proteins. These ‘amyloid’ plaques are a feature of Alzheimer’s, Parkinson’s and Huntington’s diseases as well as the spongiform encephalopathies. It could be a side effect of the brain normally permitting regulated prion-like polymerisation events during memory formation. First author on papers – Shorter, Lindquist
Mitochondria inheritance
mitochondriaMitochondria are little energy factories within cells; they do the sugar-oxygen-to-carbondioxide-energy work. They are descended from bacteria which can no longer live freely without supplies from their host cells. When a cell divides about half the mitochondria go to each daughter cell. An animal gets its original group of mitochondria from the egg. The mitochondria divide in two as required and contain a small amount of DNA that duplicates at each division. So they are a separate inheritance system from that of the cell nucleus. They only pass down the maternal line. (Some genes need by mitochondria are in the nucleus but this does not change the general picture). Malfunctions of the mitochondria leave cells without enough energy. There are diseases carried by mitochondria: forms of cancer, diabetes, infertility, and neurodegenerative diseases. First name on paper – Lee.
The missing heritability
There are traits where patterns of inheritance within the population strongly imply that most of the variation is due to genes, but attempts to identify specific genetic variants that are responsible for the variation have failed. (height is 80-90% heritable but no genes appear to account for very much of this) This would mean that there are innumerable variants widely distributed in the population. This 'little' problem has not been solved yet and there are arguments about even what the problem is. The older theories of heritability need to be updated.
Viruses in the DNA
In the course of evolution retroviruses have made themselves a home in our DNA. We all carry ancestral DNA derived from viruses in our genome. There are roughly 100,000 copies of endogenous retroviral DNA in our genome. It got there because: a virus needs to infect cells and use their machinery to replicate. Retroviruses carry RNA and they manage to get the RNA code translated to DNA and incorporated into the genome. (Or they carry DNA which is directly incorporated into the genome.) Occasionally, the virus invades a reproductive cell (egg or sperm) and then it is stuck in its DNA. If this cell becomes part of a fertilized egg, the resulting animal and its descendants will carry this virus' code. This is the source of transposons, jumping genes, imports of bits of genetic material from other animals picked up in passing through other genomes and other marvels and dangers. First author on paper – Emerman
Retrotransposons
Buried in the genome are a great many virus-like stretches of DNA that epigenetic mechanisms suppress with methylation. But this is not always successful and a retrotransposon can escape its block. These virus-like bits of DNA can also move about in the genome. It is likely that they can cause fetal development problems and diseases. - first author on paper - Ekram
Viral expression in the placenta
Viral genes in the genome are usually blocked. But in the cells of the outer layer of the placenta, some are translated and transcribed. The explanation is that retroviruses have genes for proteins that can debilitate the immune system and the placenta takes advantage of these. Making these proteins protects the fetus (a foreign parasite to the mother's body) from attack from the mother's immune system. Another characteristic protein from viruses is one that can merge cells together in one membrane. This is useful to form the barrier between maternal and fetal blood. First authors on papers – Dunlap, Dupressoir
Jumping genes
Jumping genes seems to happen more in the brain than other tissues. They can paste copies of themselves into other parts of the genome and alter the functioning of the affected cell, making it behave differently from an otherwise identical cell right next to it. Many such insertions in many different cells would be expected to yield subtle or not so subtle differences in cognitive abilities, personality traits and susceptibility to neurological problems.
The jumpers are mostly retrotransposons and copy themselves rather than move. The long interspersed element 1 (L1) hops frequently because it encodes its own machinery for spreading. First it is transcribed into RNA which travels out of the nucleus and is the template for constructing proteins. The proteins and the RNA strand form a molecular complex which re-enters the nucleus. It makes a nick in specfic sites in the DNA. Then it copies the RNA into DNA (like a retro virus) and inserts the DNA into the genome at the nick. Such reverse transcription, from RNA to DNA, is familiar to many people today as part of the way that the HIV virus gets a DNA copy of its RNA genome to take up a permanent home in the genome of the cells it infects.
Retrotransposition often fails to run its course, which produces truncated, nonfunctional copies of the original L1 DNA. Sometimes these snippets (or the whole L1 copy) have no effect on a protein-coding gene. They have made the nick in a safe place. At other times, though, they can have any of several consequences, both good and bad, for a cell’s fate. They may, for instance, drop into and thus alter the protein-coding region of a gene.  This maneuver can lead to creation of a new variant of the protein that helps or harms an organism. Or this positioning may stop a given protein from being made. In other instances, the newly pasted DNA may fall outside of a coding region but act as a promoter (a switch that can turn on nearby genes) and alter the level of gene expression—the amount of protein made from the gene—with, once again, good or bad results for the cell and the organism.


Myths about eating disorders
There is a lot in ignorance about eating disorders. It is found in the general public, journalists, and even doctors. It is found in the sufferers of eating disorders, their families and their friends. A suffer may not known a single person that is not mis-informed on the subject. This really does get in the way of sufferers getting effective help.
Many believe that eating disorders are minor disorders of white, vain, teenage girls. This is not helpful for the sufferers that are from other races, adults and children, or male. As far as being a minor condition, only 3 % in a study thought that anorexia or bulimia could cause physical harm, whereas these can often actually be fatal.
Even when a sufferer is visiting a doctor or clinic, their disorder can often be missed. If it is noticed it is often not treated. The sufferer is simply told to eat better.
There is a stigma that is common in the reaction to eating disorders: hostility, disapproval and blame. This actually dissuades sufferers from getting help or even searching for it. A study of articles on the subject in prominent American newspapers/magazines showed:
Classification of the problem: about half were in the Arts and Entertainment section, but only 13% in the a Health section
Causes identified: about half put blame on the parents, commonly mentioned was psychological causes (low
anorexiaself-esteem, stress), often the cause was framed as the sufferer's simple personal decision, only 2 articles (1%) even mentioned the possibility of a biological or genetic cause. caption
Treatment and outcomes identified: only 21% mentioned treatment as a solution, less than 10% framed the condition as worthy of medical treatment, only 11% mentioned any medical complications, there was an assumption that recovery was more common than it actually is. Some articles portrayed recovery as simple (snapping out of it, being inspired, having a dream, making peace).
There is a small difference between the American and British press. Clinical complications are 4 times
more likely to be mentioned in UK versus US news and treatment twice as often. In the UK recovery is much less often discussed and in a less optimistic way. In general the UK press is better but not by much.
This sort of reporting is almost criminal. Anorexia is known as the most fatal mental illness – between 5 and 20% of its sufferers die from it. Those that live have damage to almost every bodily system after recovery. And this is one of the problems – it is thought of as a mental illness. It may or may not be a mental illness to start but it soon becomes a physical illness and a very intractable one.
I personally do not believe that the majority of cases even start as a mental illness. The diagram shows a particularly reasonable mental illness model illustration of the disease but it does not include a number of important non-mental factors (taken from scientific pap
er Kaye 2009). Even this level of honest reporting is extremely rare – almost unknown except in scientific papers.
The attitude that people have of anorexics is similar to their attitude towards the obese – except it is more serious for anorexia & bulimia – blame the victim.


The polio affair
Americans and Brits and many other Europeans were extremely surprised that Pakistan arrested Shakil Afridi, the doctor who tried to help the CIA to find Osama bin Laden. They were furious when he was convicted and got a 33 year sentence. My immediate reaction was, "WTF? Why jail him? Give him a gold star."
But then I found out that the World Health Organization is very upset – very, very upset - with the doctor and the CIA. Doctors without Borders was also vocal in condemning Afridi and the CIA for putting essential health services, public health programs and humanitarian aid under suspicion in many parts of the world. The background is that WHO is trying to eliminate polio from the face of the earth and they are getting close. Polio is now confined to three countries: Pakistan, Nigeria and Somalia. Getting the children vaccinated in these countries has proven difficult. In all three there is an urban myth that vaccination is an Western (or American or CIA) plot to harm their children, sap the strength of their culture etc. WHO makes slow but steady progress against this prejudice. It was within a year or year and a half of getting over the peak and travelling down hill in the project. But they were still in danger of the disease getting out of their contentment if they could not continue with the vaccinations in any of these three countries. To WHO a lot was at stake. They could not afford to lose trust they had earned over many years.
So what happens: the CIA organizes with the help of a local doctor a fake vaccination program. Could they have done anything more calculated to damage public health programs in general and especially in Muslim countries and to do with polio? Is nothing out of bounds? And the results are as you would expect. “They (tribesmen) consider us CIA agents, who under the guise of anti-polio campaign, are there to look for other Al-Qaeda and Taliban leaders,” said Gulrez Khan, a Peshawar-based anti-polio worker. “It’s been over ten months since the Al-Qaeda Chief Osama Bin Laden is dead, but his ghost is still haunting our efforts not only to persuade the people in the country’s northwestern parts, particularly in the tribal belt, to get their kids vaccinated, but also to move freely.” Public health workers lifes have been put in danger, many children are not being protected from polio and the WHO program is been stopped in its tracks.
Actually, I doubt that the polio-eradication aspect that a lot to do with Pakistan's view of the doctor's crime but it certainly was the root of WHO's view. A doctor should really have known better. There is kind of an unwritten rule, perhaps it's even written somewhere, that fighting soldiers do not use the Red Cross as camouflage. Well, they should know better than use public health services too.
Still it seems that Pakistan was lenient towards the doctor. There was some leeway in how he was trie
skeletond. He has been charged under a British-era regulation for frontier crimes that unlike the national criminal code does not carry the death penalty for treason. Under normal Pakistani penal law, Dr. Afridi almost certainly would have received the death penalty – or so I have read.

Cost of erect posture
Illustration shows the ills that we get from being bipedal.





Maybe good news
Finally some good new on Alzheimers – it will be diagnosed much earlier. This means that there may be treatments that can be started before great damage has been done to the sufferer's brain. Well that is what the headlines say but it is still a maybe. The work was done on people who were of risk of a particular inherited form the Azheimers and now it has to be tested on a broader sample of people. The reason that these particular people were studies is that the researchers were fairly sure they would get Alzheimers and of when they would show symptoms. It will be years before it is a reliable diagnoses for all or maybe it will not turn out to be one.
But still it is good news, making it easier to understand the disease through new lines of research.
What was found was that 25 years before symptoms a particular chemical (Amyloid-beta 42) declines in the cerebral spinal fluid. 15 years before symptoms there are increases in tau protein in the CSF. Lower metabolism in the brain is seen 10 years before symptoms. Some impairment (not seen as distinct symptoms) can be seen 5 years before symptoms and diagnosis is on average 3 years later.
If this or similar patterns happen in other sufferers than there is ample time to treat the disease before much damage is done – assuming there are treatments. And treatments are more likely if the course of the disease is better understood. With the 'but' that the causes, course and treatments for inherited and non-inherited Alzheimer may not have that much in common.
Misfolded Protein Diseases

This is a fairly newly discovered type of disease mechanism, misfolded proteins, and its study may result in treatments for some difficult to treat conditions. Diseases that have (or are suspected to have) this mechanism include:
in humans:
Kuru (misfolded PrP protein)
Creutzfeldt-Jakob disease (misfolded PrP protein)
Alzheimer's disease (misfolded beta amyloid and tau)
Parkinson's disease (misfolded alpha synucein)
Huntington's disease (misfolded huntingtin)
Systemic amyloidosis
Cystic fibrosis (misfolded CFTR protein)
Gaucher's disease (misfolded beta glucoscerebrosidase)
Marfan syndrome (misfolded fibrillin)
Fabry disease (misfolded alpha galactosidase)
Retinitis pigmentosa 3 (misfolded rhodopsin)
some cancers (misfolding of tumour suppressor proteins)
Type 2 diabetes (misfolded amylin)
Hereditary transthyretin amyloidosis (misfolded transthyretin)
Gerstmann-Straussler-Scheinker Syndrome
Fatal Familial Insomnia
in animals:
Bovine spongiform encepalopathy -Mad Cow Disease (misfolded PrP protein)
Chronic Wasting Disease (misfolded PrP protein)
Scrapie (misfolded PrP protein)
Transmissible mink encephalopathy (misfolded PrP protein)
Feline spongiform encephalopathy (misfolded PrP protein)
Ungulate spongiform encephalopathy (misfolded PrP protein)

The mechanism has only recently been identified. The unusual transmission of Kuru was shown in the 70s, the nature and name of 'prion' is dated at 1982, and it is only in the last couple of years that the possible scale of misfolded proteins has surfaced. All
ERof these conditions have no cure and most have no effective treatment. Many are fatal. A treatment type that would work for most of them would be a 'wonder drug' – many researchers have been attracted to this possibility.
So why are proteins folded and what is dangerous about misfolding? Protein do the majority of the work in
a cell – they catalyze chemical reactions, give stability to structures, bind and transport molecules, recognize and identify other proteins and so on. Unlike how we envisage most molecules, proteins are fairly flexible and that is part of how they work. But in order to operate within the range of motion that is needed for their function, they must be folded corrected to start.
Proteins are made of amino acids that form a long chain with the sequence of various amino acids dictated by the sequence of codons in DNA and then RNA. Each amino acid has a different shape and chemical nature and so sequence of them in a chain has an ability to take up shapes that are useful.
So the making of a protein has the following steps. A messenger RNA string (the information) hooks up with a ribosome (a protein/RNA factory for making protein) and a chain of amino acids is produced by indexing down the codons of the RNA and adding each matching amino acid to the growing protein chain. The chain is inspected by and chaperonemay be forced into a particular folding by other proteins called chaperons (illustrated with GroEL). Well folded proteins are allowed to go do their work and proteins that refuse to fold correctly are destroyed. Of course things can go wrong at every stage and also after the protein is correctly fold it may be later damaged.
hemoglobinHere an animated illustration of part of a working hemoglobin assembly. It has two possible working configurations. One takes and holds oxygen (oxy shape) and the other gives oxygen up (deoxy shape). The configuration depends on many factors that result in oxygen take up in the environment of the lungs and release in the conditions in the tissues. If the chains in hemoglobin were not in the right conformation they would not flip between the oxy and deoxy shape and therefore could not deliver oxygen to the body.


Spongiform encephalopathies or prion diseases involve a protein found in all mammals largely in the brain. The protein is slightly different in each animal. This type of disease is either infectious or occurs by a mutation. The prion protein has a globular domain with a working end sticking out along with an anchoring tail that holds it to the outside of a cell. The globular part can be folded in two ways: one with alpha helices (normal) and the other with a beta sheet (disease causing). These are common structures in all proteins. The disease causing form of the prion can convert the normal form to the disease form. So the introduction of the disease causing form slowly destroys all the brain's normal form by converting it to the disease causing form. prionIt acts as a sort of chaperone. The cells with diseased prion die and this results in the sponge like look of the brain, full of holes. The brain is somewhat defenseless because the disease causing form is resistant to protein destroying enzymes. There are accumulations of the abnormally folded protein in the brain. The disease starts in an animal when it eats disease causing prion or when they have a mutated prion which can occasionally flip from a normal configuration to the dangerous one, called sporatic disease.
In the case of Bovine SE or mad cow disease, a cow can get the disease from eating food manufactured from diseased animals. The normal sterilization procedures will not destroy the prion so it is important not to include animal scraps in the food. Occasionally a cow gets the disease from a spontaneous refolding to give a sporatic case of mad cow disease, rather than a infection case. The bovine prion is similar enough to the human one that humans can get SE from eating diseased beef (but not often). The sporatic human SE has the same name, Creutzfeldt-Jakob disease. Humans can also get SE from canabalistic eating of human flesh if it is diseased with Kuru prion.

Amyloid diseases are caused by faults in the cutting of proteins so that the fragments refold into beta sheets forms which aggregate into tight insoluble fibrils. (Strictly speaking prions could be called amyloids and they do form fibrils but they are caused differently.) We start with a useful amyloid precursor protein which is found in cell membranes throughout the body but specially in neuron synapses. There are many differentalz precursor types depending on the tissue. The faulty cutting of amyloid precursors in various tissues gives rise to many different diseases. (The definition of amyloid is a bit circular – it refers to a smallish bit of protein that is cut from a larger one and that is badly folded including beta sheets in place of alpha helixes and forms insoluble aggregates called plaques.) Lets take as an example Alzheimer's disease. It has at least two causes but the progress is similar. And there are two types of plaque accumulated (beta amyloid and tau). The condition moves from one neuron to the neurons it connects in synapses, and so it steps, killing cell by cell, slowly in the brain. Each of the neurodegenerate diseases has a particular starting point in the brain and therefore a different path of destruction. For example Parkinson's destroys the motor system before the memory system but Alzheimer's goes for the memory early in the disease. The endpoints are more similar: a spongy brain filled with plaques and an almost vegetative state. The fibrils of tau disrupt the transport system that feeds the long axon of the neuron and the small aggregates of beta amyloid when they are still soluble are toxic (possibly by making holes in the cell membrane). The plaques are insoluble and not toxic. It is still a mystery how the condition starts. The illustration shows the inherited disease type which has a faulting enzyme, beta secretase, cutting the precursor.
Every organ in the body can develop an amyloid disease with cell death, plaques and loss of function. For some reason, they are more common and varied in the brain (except perhaps type 2 diabetes).

Lack of an important protein can happen because the protein is always misfolded and therefore destroyed. The protein is made, does not pass inspection and is digested into its amino acids. The disease is caused by the lack of that protein. An example is cystic fibrosis, lack of the protein CFTR. Many cases of cystic fibrosis are due to inheriting a defective gene for CFTR from both parents. The protein does not fold correctly and is destroyed. CFTR is the chloride gate in the outer membrane of cells. It is required for the correct production of sweat, mucous, and digestive juices. Other diseases of this type are far rarer that cystic fibrosis because the defective genes are not as common in the population (Marfan, Fabry, Gaucher, retinitis pigmentosa).

What about prevention, treatment and cure of these diseases? For prions, as well as regulations of what can be fed to animals and what animals can enter the human food chain, there is work in synthetic chaperones which could correct the folding of prions in the brains of sufferers. Those diseases like cystic fibrosis and Huntingtons which are plainly genetic in origin (not just affected by a more minor genetic predisposition) maybe treated with gene therapy to introduce a healthy gene to replace the faulty one. The amyloid diseases that are not genetic have a great many causes and might have many individual treatments. One interesting idea is to stop a particular effect of neural inflammation, which seems to be common at the start of Alzheimer's, Parkinson's and similar diseases. It is thought that this kind of treatment could be used for MS and stroke which also start the damage chain with inflammation.

Computerized health
Computerizing health services is something I really endorse – with a lot of buts. It seems like a lot of money is spent on systems that do not work. There was a recent study (Black and others, PLoS Medicine) of 53 systems which concluded:
“There is a large gap between the postulated and empirically demonstrated benefits of eHealth technologies. In addition, there is a lack of robust research on the risks of implementing these technologies and their cost-effectiveness has yet to be demonstrated, despite being frequently promoted by policymakers and “techno-enthusiasts” as if this was a given. In the light of the paucity of evidence in relation to improvements in patient outcomes, as well as the lack of evidence on their cost-effectiveness, it is vital that future eHealth technologies are evaluated against a comprehensive set of measures, ideally throughout all stages of the technology's life cycle. Such evaluation should be characterised by careful attention to socio-technical factors to maximize the likelihood of successful implementation and adoption.”
Tens of billions are being spent without the results expected. In the present state of computer engineering, I think that small systems can and are produced that work well and are cost effective. These systems are created by one or a small group of minds and those minds actually know the problem is and how it has to be solved in order not to cause new problems. The larger the system, the more money it is costing, the less the people in charge actually know what is needed, and the more people involved – the higher the risk that a useless white elephant is being produced. The bigger systems should be better by all sorts of criteria, but they rarely are. Once you leave the small group that talks to each other daily and who all know both computer system development and the processes being computerized – then you need a more and more complex structure to eliminate errors and misunderstandings. To date these project management structures have not worked well. I think I know some of what is wrong with them but I have no idea how they could be fixed.
When billions are played out of new big health systems, it seems to be luck whether a system gets built, and if it gets built then further luck whether it works and if it works yet further luck whether it was cost effective. It would have been far safer to go for small or medium sized systems.

The obesity paradox
There is something called the obesity paradox – but it is only a paradox if you start out with the premise that obesity is the root cause of much illness and that being overweight is never advantageous. Recent studies are said to be paradoxical because they do not conform to this view.
Correlation is not the same as cause. If A often occurs with B, it can be that A causes B, or that B causes A, or that C causes both A and B. But anytime a disease condition correlates with obesity, the billing is that obesity causes the disease. Being overweight or obese is listed as a risk factor for metabolic syndrome (combinations of high blood pressure, insulin resistance, high blood sugar, high cholesterol) and type 2 diabetes. So people are being told that they have metabolic syndrome because they became overweight.
A study followed over 43,000 people for 24 years and found that 46% of the obese were metabolically healthy with no sign of metabolic syndrome. “The findings show there is a subset of obese people who are metabolically healthy -- they don't suffer from conditions such as insulin resistance, diabetes and high cholesterol or blood pressure -- and who have a higher level of fitness, as measured by how well the heart and lungs perform, than other obese people. Being obese does not seem to have a detrimental effect on their health.” So being obese is not 'the' cause of ill health. (Although I would guess that being obese could contribute to making metabolic syndrome more severe and that metabolic syndrome can contribute to making obesity worse.) So, what is the difference in the fat and healthy group from the fat and unhealthy group. They are fit – that is it – they are fit. “Based on the data that our group and others have collected over years, we believe that getting more exercise broadly and positively influences major body systems and organs and consequently contributes to make someone metabolically healthier, including obese people. In our study, we measure fitness, which is largely influenced by exercise.” Lack of exercise may be an important risk factor, maybe even 'the' risk factor.
Another paradox comes from the idea that if someone has angina, a heart attack or other cardiac problems than they should loss weight if they are overweight as part of their recovery. This is a bad idea. This study followed 64,000 people recovering from cardiac events for 4 years. "We found that patients who were underweight with a body mass index (BMI) of less than 18.5 kg/m2 had the greatest risk of dying. Their risk was double that of normal weight patients, who had a BMI of between 21 and 23.5 kg/m2. Compared to the group with lowest risk -- those with a BMI of 26.5 to 28 kg/m2, they had three times the risk of death." So the fat were doing better than the normal and they were doing better than the thin. But they found that the really morbidly obese were doing as bad as the thin. “Actually some evidence suggests that weight loss after ACSs might in fact have a negative effect.” But we do know that a supervised exercise plan is very good for cardiac recovery.
Actually there is no paradox. The important thing is to be fit.

Antibacterial Soaps
Triclosan is a widely used antibacterial chemical in soaps, deodorants, mouthwashes, toothpaste, clothes, bedding, carpets, toys, trash bags, etc. It is not a safe chemical because it interferes with muscle contractions. It is pervasive in home and in the environment – it is found on household and hospital surfaces; human blood, urine and breast milk; rivers, lakes and water ways; the tissues of aquatic life like algae, fish and dolphins.
Experiments show that within the level of triclosan found in our world, it is able to affect muscle including heart muscle. It impairs the calcium channels in muscle cells and calcium is important in muscle contraction. They showed a 25% reduction of heart function in mice. In fact, triclosan has enough effect of cardiac muscle that it should rightly be reclassified as a cardiac drug. The mice also had a reduced grip. Testing fish showed that triclosan reduces fish swimming speed, both normal speed and maximum speed. It has also been shown to have a disruptive effect on reproduction hormones and signaling activity in the brain.
Triclosan can be useful in some situations but being included in products where it is not doing useful work is definitely more harmful than helpful. For example, ordinarily the washing of hands, in a ordinary soap is just as good as using anti-bacterial soap.


New med for my joints
My knees, hips and shoulders are prone to joint pain. One knee in particular was broken in the 70s and has been somewhat of a bother ever since. It was the first joint to get arthritic. Then the other knee showed sympathy. I broke my shoulder in the early 90s and it is very useless. Now both shoulders are sensitive to cold and overwork. In the last 10 or so years, my hips have started to give me problems. I suspect it is because I am overweight and sit a lot.
In the last while I had thought that I had a good way the handle my joints. They were improving. I could walk without a cane and I was cutting back on the dosage of the things I took. I was walking up in the morning with more and more ability to move. I was also getting some exercise and slowly losing weight.
Now I have been put back. I have very mild but constant pain in my knees and hips – I can more or less ignore this but it is a change for the worst. I now need a cane for my 20 minute walk and I have a fair bit of pain. I have been told by my doctor and the specialist not to take any NSAIDs (non-steroid anti-inflammatory drugs) because they are hurting my gut. I had little idea how much I relied on Ibuprofen until I stopped taking it.
My doctor gave me Avocado Soy Unsaponifiables saying that they would go to the root of the problem.
Apparently, the French medical system has been studying it for years and believes it is effective and without serious side effects. “Studies in the laboratory have found that ASU can reduce the production/action of various joint inflammatory substances and can prevent the destruction of joint cartilage caused by chemicals called interleukins. ASU can also stimulate the production of collagen, a natural component of tendons, joints, ligaments and muscles. Studies in animals have confirmed these findings and discovered that ASU stimulates the production of specific factors in the joints that can prevent cartilage wearing down and can help repair damaged cartilage.”
There is a compound called aggrecan which is a structure on which some of the cartilage in joints is built. The aggrecan protein can hold in place up to 150 chondroitin sulfate chains and 60 keratan sulfate chains. A number of these groupings, up to 100, then interact with hyaluronic acid to product a massive chain called an aggregate. These aggregates give the osmotic pressure of the cartilage in a joint.
When there is no load on the joint the cartilage takes up water and swells to its maximum. When weight or work compresses the cartilage, the water is squeezed out. The amount of water in the cartilage depends on the ratio of osmotic force and compressive force. Cartilage should have something like 75% water. Aggrecan is the core of cartilage health. (This is why supplements of glucosamine and chondroitin are helpful – they form part of the aggregates). But how can we get supplements to supply aggrecan protein?
University Hospital in Liege Belgium reported in 2003 that a phytosterol/sterolin extract concentrated from oil found tightly bound to avocado and soybean fiber could significantly increase the body's production of aggrecan. The extract blocks the action of interleukin-1-beta in causing inflammation and by doing this restores the body's production of aggrecan protein. The extract also reduces several other inflammatory factors. The body's normal digestion does not separate the oils from the fiber and therefore eating avocado and soybean is not effective (but is healthy in other ways).
Under the name avocado soy unsaponifiables (ASU), the extract has been a prescription drug in Europe for several years and has undergo several trails. As far as the French medical system is concerned, it is the main medicine for mild arthritis and NSAIDs are now a no-no.


Genetics textbooks will have to be rewritten

In the good old days, genetics was the simplest area of biology. Some simple rules and elementary algebra was all that was involved. When the genome was completely read, we would understand what genes produced what effects and how. But now that it has been read, all is confusion. The genome is not at all like what was expected. (We should have know from the past that biology is never neat, simple or straight-forward.)
There is epigenetics! I wrote about this before, but as an addition to the main idea of genetics. It now appears that epigenetics is the main event and conventional genetics takes a back seat. Gone is the law that the environment cannot change the genetic material. Gone is the notion that there is junk DNA. Gone is the idea that RNA is just a temporary carrier of genetic information. The search for the genes responsible for many conditions/traits has been disappointing. Looking through most of the genes has found only a small percentage of the inherited component for complex traits. If epigenetics is responsible for the more substantial fraction of inheritance then there has to be a revolution in thinking.
Until recently epigenetic memory was only DNA methylation or histone modifications and these were erased in the germ cells and so were not passed on to offspring. It turns out that the erasure is not that complete and that there is another path, the passing down of actual RNA molecules. So RNA that was created by one genome (say the mother's) can be found in an offspring that lacks the information in its genome to make that RNA. Recently it was comprehensively shown that an gene mutation that causes a particular tumor in mice in a grand maternal ancestor can give effects for at least three generations in male mice that do not carry the mutation.
Here is a quote. “Thus, if RNA editing can alter hardwired genetic information in a context-dependent manner, and thereby alter epigenetic memory, it is feasible that not only allelic but also environmental history may shape phenotype, and provide a far more plastic and dynamic inheritance platform than envisaged by the genetic orthodoxy of the past century. Morever...RNA, more than DNA, may be the computational engine of the evolution and ontogeny of developmentally complex and cognitively advanced organisms.” - Mattick
This revolution has only just started.

Dealing with stress
Stress is cruel to the body but it is not that simple. People used to say that there was good stress that helped people like exercise does and then there is bad stress that kills you. But it is not really that either. It is how people deal with stress that is important.
A big longitudinal study has shown that.
"Our research shows that how you react to what happens in your life today predicts your chronic health conditions and 10 years in the future, independent of your current health and your future stress. For example, if you have a lot of work to do today and you are really grumpy because of it, then you are more likely to suffer negative health consequences 10 years from now than someone who also has a lot of work to do today, but doesn't let it bother her... The team found that people who become upset by daily stressors and continue to dwell on them after they have passed were more likely to suffer from chronic health problems -- especially pain, such as that related to arthritis, and cardiovascular issues -- 10 years later."
So what besides a person's basic personality can allow them to react well to stress?
"Our research shows that people age 65 and up tend to be more reactive to stress than younger people, likely because they aren't exposed to a lot of stress at this stage in their lives, and they are out of practice in dealing with it. Younger people are better at dealing with it because they cope with it so frequently. Likewise, our research shows that people with lower cognitive abilities and education levels are more reactive to stress than people with higher cognitive abilities and education levels, likely because they have less control over the stressors in their lives."
This sort of balances the amount of stress. Younger people, for example, have more stress than older people; people with higher cognitive abilities have more stress than people with lower cognitive abilities; and people with higher levels of education have more stress than people with less education.
So avoid having more stress than you can deal with keeping. Keep cheerful and calm. You'll thank yourself 10 years done the road.

Why is there a flu season?
Flu virus floats in the air in tiny droplets of mucus produced when people cough and sneeze. The droplets can stay in the air for hours and hours because they are so small. These little droplets are more infective in flu season, that is winter in the north and south but the rainy season in the tropics. The reason for this pattern is that the little droplets can evaporate and so become smaller and more concentrated. When this happens in the northern winter when inside humidity is very low, the droplets completely dry, and they are very infective when dry. On the other hand in the rain of the tropics, they cannot evaporate at all. But in between not evaporating and quickly drying completely, what happens is partial evaporation. In the partial case the chemicals in the mucus become quite concentrated and these chemicals interfere with the infectiousness of the virus.

 
Biological Energy: how our muscles get energy
How biochemistry works
Biochemistry is very complicated. Here is a very, very simplified diagram of its pathway. A full diagram would take a whole wall. Don't be scared, we are not going get lost in this diagram.
chart

Molecules are responsible for all the things that living things do: grow, eat, digest, get rid of waste, move, reproduce, sense the world, and on and on. Often it is their shape and the way they change their shape that is important. 
mitochondria
People say that we 'burn' sugar for energy. Of course, this is not strictly true – there is no flame. But the  process is the same in the sense that the sugar combines with oxygen, becomes water and carbon dioxide, and some energy is 'liberated'. The difference is that in the cell the energy is trapped rather than liberated.  The energy is stored in a particular molecule (called ATP). Then this ATP molecule is used by all the things in a cell that require energy. It is often called the energy coinage of the cell.
In plants and animals, the making of ATP while burning sugar is done in little cells within the cell. They are called mitochondria. They are like cells because they once were free-living cells and have their own outer membrane, their own DNA, and they multiply by dividing in half. A cell will run out of energy if it does not have lots of healthy mitochondria. Here is what they look like in a cut away picture.
These are often called the cell's power stations.
muscleOne of the uses of ATP is to power muscles. Muscles have long fibers that contain two sorts of strands. The one type can 'climb' along the other in order to shorten the total length of the fiber and then can relax and lengthen the fiber. Here is a picture of a muscle cell.
A muscle contracts when it gets commands from nerves. The nerves do not enter the muscle cell but makes a special junction on the surface. There is a little space between the nerve and the muscle. When a nerve impulse arrives, packages of a chemical are allowed into the space and the muscle cell reacts to that chemical on its membrane. Things then happen to make the muscle fibers contract. Here is a picture of the neuromuscular junction.









junction


So that is the general idea. (1) We take in food, digest it and transport it to cells. (2) We breath and transport the oxygen to cells. (3) Mitochrondria in the cells take in the food, oxygen, ADP and produce from them carbon dioxide, water and ATP. (4) The ATP goes to places in the cells where energy is needed, then it is used to do work while changing back to ADP. (5) If the cell is a muscle cell and if it is activated by a nerve, the ATP is used to contract fibers.
The reason that the biochemical diagram is so complicated is that there are many steps to each part and there are many other things that help, hinder or regulate each step. These other things are not included in the simple diagram. One should be mentioned here: calcium ions (Ca++). These are calcium atoms that have lost 2 electrons. They are important in almost everything that happens in the cell including mitochrondria and muscle fibers. Ca++ is one of the chemicals called 'second messengers' because they carry messages from the cell's surface where hormones and other chemicals are recognized. Ca++ is held in little sacs when not needed.
Now we can look in more detail at some parts of this process.
Making ATP
ATP is how adenosine-5'-triphosphate is usually referred to. Adenosine (the A) is a common molecule in the cell and a phosphate group (the P) can be added to it to give AMP (M for mono), then another can be added to give ADP (D for di) and a third gives ATP (T for tri). Adding each phosphate takes a good deal of energy. It is an 'up hill' reaction. When a phosphate is removed it is a 'down hill' reaction and so can force other molecules to change in some way (like shape).
There are many ways to make ATP from ADP but we are only interested in two of them. In the biochemical diagram on the first page, there is a line across the middle: Glucose 1P to glucose 6P to fructose 6P to glyceraldehyde 3P to pyruvate. This is the way glucose from glycogen (which is how glucose is stored in muscle) is changed to pyruvate. Pyruvate is what mitochrondria need as fuel. Fats and proteins can also enter this pathway and become pyruvate. The path is called glycolysis. What is important about this pathway is that it feeds the mitochondria and also can produce a small amount of ATP itself without the need for oxygen; 2 or 3 molecules of ATP are made while one glucose molecule becomes pyruvate. This pathway works fine when the mitochrondria are working. But the cells cannot stand a build-up of pyruvate. If the mitochrondria cannot take in the pyruvate then the cell must convert the pyruvate to lactate in order to protect other reactions. That is in the diagram beneath pyvuvate. In muscles, if there is a lot of work and the lungs/heart cannot deliver enough oxygen, then lactate will build-up. This is what causes the pain and fatigue feeling after prolonged exercise which goes away after enough oxygen is delivered (see description of lactate build-up at end). When there is enough oxygen delivered then the lactate is changed back into pyruvate and used by the mitochrondria. That is how it goes when everything is working as it should.
krebsAnother pathway is the one in the mitochrondria. It is a bit like a water wheel. Molecules go around in a cycle. It is the circle in the big diagram to the right of the glycolysis line. Here it is in more detail.
This looks very complicated but the general idea is simple. Pyruvate has three carbons and so we want to get those three carbons to be in three molecules of carbon dioxide. It loses one to become acetyl which has 2 carbons. The acetyl is added to a 4 carbon molecule and then 2 more carbons are lost along the wheel. Now we are back at the 4 carbon molecule and another acetyl can be added.
One molecule of glucose has 6 carbons and gives two molecules of pyruvate. In the mitochrondria the 2 pyruvates produces 4 ATP, 6 NADH, 2 QH2. Each of the NADH is used to produce 3 ATP. If all is working perfectly one molecule of glucose should result in 30 molecles of ATP.








membrane


























Now we get to the tricky bit and the reason why the ATP production has to be inside a membrane, the mitochrondria's. A biological membrane is an electrical insulator and so it can have a different charge on the two sides of the membrane. (It is an insulator because it is made of fat molecules, all lined up). In order for anything to move across the membrane, it must be helped by molecules that sit across the membrane. These are called ports, pores, gates, channels, transporters, and are big or small, complex or simple. The diagram shows the membrane we are interested in. Moving electrons across the membrane is linked physically to adding a phosphate to ADP. The two reactions are tied together like a pair of gears, one turning the other. This is a complicated process so I will not deal with its nitty-gritty. The important thing here is how important healthy membranes are to getting this energy rather than wasting it. (Think omega 3, olive oil, unsaturated and the like.) NAD needs vitamin B3 (niacin) to make the N part of the name. And, of course, there are many enzymes and they involved  various minerals, especially magnesium, zinc and iron. They can also be poisoned by many poisons. The mitochrondria also produce their own poisons especially if they are driven too fast. They are called oxidative radicals, so antioxidants can help mitochrondria when they are working hard (Vit A, Vit C, magnanese etc.)
The cell does not store ATP; it is made as needed like modern 'just in time' supply chains. How hard the mitochondria work depends on how much ATP is needed at that time. So the regulation of the mitochrondria is important. If they are not turned on they cannot produce ATP. Calcium is the key. It is Ca++ that is the major control on mitochrondria and the production of ATP follows closely the amount of Ca++ in the mitochrondria. Too much Ca++ forces the mitochrondria to work too fast and damages it. So it is important to have calcium in the diet and vitamin D is need to absorb the calcium from the gut and regulate its use in the body.
Using ATP in muscle
Muscle cells are very long with connective tissue surrounding them to connect them to other cells and to bones. Each cell has many nuclei which is an oddity – most cells have one. They have many mitochrondria, stores of glycogen to get glucose from, and a lot of stored Ca++. There was a diagram of a muscle cell near to start.
fiberMuscle has thin filaments called actin and thick ones called myosin. The myosin filaments have knobs along them and the knobs are where bridges are formed between the two types of filament.
It happens a bit like rowing a boat. First a molecule of ATP attaches to a myosin knob and becomes ADP. This is called energizing the myosin bridge, like lifting the oar out of the water and moving it back. Next the myosin bridge connects to the actin. This is called attachment, like dropping the oar back in the water. Then the cross bridge changes its angle and loses its ADP. The movement of the cross bridge produces the force of the contracting muscle, like pulling on the oar to move the boat. Finally a molecule of ATP is added to the bridge and the myosin knob disconnects from the actin, like lifting the oar out of the water. As you can see we are back to where we started with an energizing myosin bridge ready to attach again at the original angle. What has happened is the the two filaments have slid pass one another by a small amount. This is happening all along the fibers when a muscle is contracting. Each little tug uses an ATP molecule. Here is a diagram of one band along a muscle fiber in a relaxed and a contracted state.
There is another molecule that prevents this contraction from happening. The attachment points on the actin are covered by this other molecule so that the bridges cannot form. But when Ca++ is present around the filaments it removes this cover so that contraction can happen. The covering molecule would sooner stick to Ca++, if it is available, then stick to actin. So whether a muscle contracts or not depends on regulating the amount of Ca++. This is why when the muscle has too much Ca++ it can  cramp.
The Ca++ is held in a structure called the sarcoplasmic reticulum that is like a sleeve around each muscle cell and has sacs of Ca++. When a nerve activates the fiber (this also takes both Ca++ and ATP in the nerve to do this), the change to the cell membrane causes the sacs of Ca++ to open channels and let the Ca++ out. When the contraction is done, the Ca++ is pumped back into the sarcoplasmic reticulum. (This uses ATP.)
Thus the nerve signal supplies Ca++ which revs up the mitochondra to supply ATP and takes the brakes off the actin. Then the muscle contracts.
Additional Notes
When I was writing this there were places where I thought, “I should mention whatever”, but it would interfere with the flow and make it harder to understand. So I am putting them here at the end.
Lactate build-up
If you look up lactic acid you can see some very serious things but they don't all apply to lactate build-up in muscle. High amounts of lactate in muscle increase the acidity because it forms lactic acid and that acidity interferes with the production of lactate. It is a sort of feedback. Even the small amount of ATP that is made getting from glucose to pyruvate is not made. This slows the muscle. The 'burn' of the acidity and the 'fatigue' from lack of energy is a defense against doing harm during extreme exertion. Some people think that the lactate is the cause of later pain but it is not. Lactate has little to do with the tenderness and stiffness that follows over-exertion a day or two after the exertion.
Lactic acid in muscle is one thing but in the blood it is more of a problem. Lactic acid at high levels in the blood can cause nausea, headache, disorientation and other more severe symptoms and damage – this can occur in many ways other than exertion (for example a heart attack).
Glycogen
The muscle stores a polymer of glucose called glycogen (sometimes called animal starch). It is made in the liver for the whole body and in muscle for its own use. It is made in small quantities compared to fat which is the main form in which the body stores fuel. Glycogen is faster to use than fat. The muscle does not store a great deal of glycogen. It is used especially for quick response to unusual demand, and also for the small amounts needed for background muscle tone. Exercise for any length of time tends to use glucose and/or fats from the blood. To look at how the muscle gets fuel supplies involves insulin and other hormones and is itself quite complex. Lethargy is often the result of lack of usable fuel. In general exercise increases the effectiveness of insulin in helping the muscle to take in glucose and fat to use or store as glycogen.
Oxidative stress
Reactive oxygen is a dangerous poison. Oxygen as a gas has two atoms bonded together and is not very reactive. But when the two atom are separated they become extremely reactive and damaging. Reactive oxygen, oxygen radicals, are a by-product of mitochrondria working too hard and the pathways for neutalizing the oxygen radicals not keeping up. A good supply of antioxidants in the diet helps the body to deal with reactive oxygen. But... you can have too much of a good thing. The cell seems to monitor how the mitochondria are doing by how much reactive oxygen there is in the cell – it should be low. If there is none, the cell senses that the mitochondria are not working at all and will turn up the activity of the mitochondria. So under normal levels of activity, too much antioxidant can make the mitochondria work harder than they need to. Moderation is the thing – lots but not silly amounts of antioxidants.
Mitochondria inheritance
Mitochondria are not inherited in the usual way. All the mitochondria in the body are descended from the mitochondria in the mother's egg. None come from the sperm. They have some DNA of their own but they also use the products of the cell's DNA for many of their parts. The number of mitochondria in a cell depends on the cell type and how much they are used. So a very fit muscle will have more mitochondria than an unfit muscle. When cells divide approximately half the mitochondria go to each daughter cell and then they quickly divide to bring their numbers back up to normal as the daughter cell expands.