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Monday, April 30, 2007

The science of cooking

Cooking is the translation of nutrition into an appetising treat. The art of cooking involves many skills which were developed intuitively and by trial and error.
Two books of interest in the field of applied food science are
1. On food and cooking: the science and lore of the Kitchen, 2004, 2nd edition author Harold McGee
Published by Scribner/Hodder and Stoughton
2. Food Chemistry by HD Belitz et al Springer 2004

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osteoporosis, vitamin D3 treatment and the prevention of falls

Fractures due to with falls is an important cause of morbidity and mortality in elderly people. Some 30% of active old people aged over 65 years and 50% of those cared for in institutions fall each year. Ninety percent of hip fractures in the elderly happen during falls and about 5% of the elderly population suffers a fall related fracture each year. This vulnerability is increased by osteoporosis which also increases with advancing age, Osteoporosis primarily affects postmenopausal women, due to the decline in bone mass and changes in bone architecture with oestrogen deficiency
Osteoporosis is an under-diagnosed and under-treated condition. In American women less than 15% of American women with osteoporosis receive treatment.. Most high-risk patients, e.g. after a hip fracture, are not treated for their osteoporosis; As the population ages, osteoporosis will become more prevalent with attendant costs of preventing and treating the disease rising
Effective methods of reducing or preventing falls and fractures in older people are needed, and vitamin D supplementation is highly recommended as a standard preventative measure in osteoporosis management." Vitamin D is essential for the maintenance of calcium homeostasis. It is synthesized in the skin after exposure to sunlight, and is also obtained through the diet. Vitamin D inadequacy is common in elderly people, particularly in countries where it is not commonly added to food.
Serum 2 5-hydroxy vitamin D (25(OH)D), reflects vitamin D status, and levels <50 nmol/l (20 ng/ml) have been associated with problems with balance. . Values <30 nmol/l are associated with decreased muscle strength. Vitamin D supplementation protects against falls that may lead to fracture. The benefits of vitamin D plus calcium (vs. placebo) have been widely studied with regard to osteoporosis. This combination is associated with a reduction in the incidence of fractures.'
However, the independent effect of vitamin D is less well understood for osteoporosis or for falls. A study by Jackson et al QJM 2007, vol 100 pp 185-192 used a meta-analysis to evaluate how supplementation with vitamin D alone affects the risk of falling, and sustaining vertebral and non-vertebral fractures, primarily in postmenopausal women. All had reduced 25(OH)D serum concentrations and subsequently received 300 to 800 IU each day.
There is some benefit from taking vitamin D3 supplements in reducing the incidence of falls which must be reflected in reduced harm to these older individuals.
Jackson et al QJM 2007, vol 100 pp 185-192

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Friday, April 27, 2007

Honey, yoghurt and Runniness

Honey, yoghurt and Runniness

When one of my children was young he would lean back after eating delicious honey laden yoghurt and say “ I love the way that trickles down my tummy” Very satisfying.
What happens and the mechanism is not one that is highlighted in Nutrition
Even the simplest ingredients can give rise to complex patterns. Mark Buchanan of the University of Oslo, Norway, and his team have tackled one family of patterns — those formed when fluids containing suspended particles flow down a vertical surface. Langmuir 23,3732-3736 (2007)
Yoghurt running down the side of a pot, for example, is cut through by vertical, branched channels, whereas honey tends to break up into wavy horizontal bands. The particle size determines which type of pattern is produced.
Smaller particles leave behind vertical channels, because the downward flow of the film becomes focused along certain paths by a feedback mechanism that amplifies flow rate. Wavy horizontal bands appear in suspensions of larger particles, as particles get trapped by random imperfections on the vertical surface and jam together to form stress bearing arches.
So I love the way that trickles down my tummy” Very satisfying.
Taken from Nature 2007, vol 446, p 587

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Thursday, April 26, 2007

Frailty in the elderlyand longevity

Frailty in the Elderly
The Japanese Centenarian Study has identified nine factors important in living to be 100-years and independent.-that is preserved activities for daily living, and good cognitive and social status)
These are good visual acuity; regular exercise; spontaneous awakening in the morning; preserved mastication; no history of drinking alcohol; no severe falls after age 95 years; frequent protein intake; living at home; and being male.
Factors militating against such longevity are a low level of exercise, a tendency to fall, and low protein intake.
Frailty is not an unavoidable consequence of accumulating years but an independent geriatric syndrome/ The clinical characteristics are anorexia, sarcopenia, osteoporosis, fatigue, risk of falls, and poor physical health. Frailty makes elderly people highly vulnerable to disability, dependency, need for long-term care, and death.’ On the basis of US studies, frailty affects about 7% of people aged 65 years or older and about 25-40% of octogenarians or those who are older.
Frail elderly people have reduced stress tolerance because of decreased physiological reserves in the muscles, bones, circulation, and hormone and immune systems.
The presence of three or more of the five Fried criteria is increasingly used for clinical diagnosis: unintentional weight loss, exhaustion, low energy expenditure, slowness, and weakness. The natural course of frailty is progressive, increasing the risk of comorbidity and disability over time. The term primary frailty can be used when the state is not associated directly with a specific disease, or when there is no substantial disability; secondary frailty when the syndrome is associated with known comorbidity such as dementia or overt cardiovascular disease .
The increasing fre­quency of obesity in elderly people further complicates the clinical picture. For so-called fat-frail individuals,-frailty is actually inside and not readily apparent. The replacement of muscle for fatfurther complicates the problem of frailty.
Frailty commonly coexists with coronary heart disease, and is associated with an inflammatory state” For effective prevention and treatment of frailty in elderly people, the syndrome (particularly the primary form) must be recognised and interventions need to start early. Screening for frailty is important.
Exercise to preserve and increase muscle mass and strength, and appropriate nutrition (especially adequate protein intake) are first-line treatments for primary frailty. Patients with secondary frailty also benefit from these along with good care of the underlying disease and palliative care in late stages of frailty and disease. Furthermore, patients with frailty should be given appropriate treatment for pain and depression. Falls and their consequences should be prevented with balance control, vitamin D, hip protectors, and adequate treatment of osteoporosis. Immunisation against influenza, pneumococcal pneumonia, and herpes zoster can protect the frail body from acute and subacute strain.
From Frailty in elderly people. Lancet 2007, 369, April 21 1328-9 by Strandberg and Pikala

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Auxin, a plant hormone and receptor function

There is a constancy in protein structure throughout biology and also small MW molecules influence their biological activity. A major protein , small molecular weight interaction occurs at receptors.
I have long felt that the hormones that are active in the other Kingdoms e.g. plants may well have import in man. Obvious, so obvious examples are the vitamins and trace elements.
A very important plant hormone is auxin. This is produced in regions of actively dividing and enlarging cells that regulate plant growth. The action is to modulate gene expression and hence cell division, elongation and differentiation. The auxins include 3-acetic acid and indole-3-acetonitrile.
Their importance is shown by their availability in every Plant Nursery Shop or Garden Centre for rooting.
How the auxin works is still being studied.

Auxin is recognised by a small family of F-box proteins including transport inhibitor response 1 (TIR1. Auxin regulates gene expression by promoting SCF ubiquitin-ligase-catalysed degradation of the Aux/I AA transcription repressors, but how the TIR1 F-box protein senses and becomes activated by auxin remains unclear. In a recent paper in Nature crystal structures of the Arabidopsis TIR1-ASK1 complex show that the leucine-rich repeat domain of TIR1 contains an unexpected inositol hexakisphosphate co-factor and recognizes auxin and the Aux/I AA polypeptide substrate through a single surface pocket. Anchored to the base of the TIR1 pocket, auxin binds to a partially favourable site, which can also accommodate various auxin analogues. Docked on top of auxin, the Aux/IAA substrate peptide occupies the rest of the TIR1 pocket and completely encloses the hormone-binding site. By filling in a hydrophobic cavity at the protein interface, auxin enhances the TIRI-substrate interactions by acting as a ‘molecular glue.
In plants, multiple phytohormone signalling pathways are now known to be regulated by ubiquitin ligases. In particular, jasmonic acid signalling requires COI1, an F-box protein with high sequence similarity to TIRT. It is feasible that COIl adopts a TIRl-like structure and possibly functions as a jasmonic acid receptor. Most of the auxin-contacting residues in T1RI are indeed not conserved in COI1. Although TIRI orthologues, so far are only found in plants, a small ligand-sensing site regu­lating substrate recruitment could conceivably be evolved in a different structural context in other human ubiquitin ligases.
An increasing number of human disorders has now been associated with defective ubiquitin-ligase-substrate interactions owing to mutations of the ligases themselves, ubiquitination substrates or upstream signalling proteins responsible for substrate priming. The regulator.’ mechanism of TIKI by auxin suggests that it is possible for small molecules to promote protein-protein interactions in ubiquitin ligases. and potentially other protein interaction systems that arc impaired by genetic alterations.
When we eat plants and presumably ingest auxins do these compounds play a necessary par in our metabolism. A wonderful research project
Tan et al 2007 Nature April 5th vol 446, pp 640-644
Guilfoyle 2007 Nature April 5th vol 446 pp 621-2

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genes and cancer of the colon

Genes and the aetiology of colonic cancer.
Sansom O J et al 2007, Nature April 5th , vol 446, 676-679
The APC gene encodes the adenomatous polyposis coli tumour suppressor protein. Mutation of the germline characterizes familial adenomatous polyposis (FAP), an autosomal intestinal cancer syndrome. Inactivation of APC is also recognized as the key early event in the development of sporadic colorectal cancers1, and its loss results in constitutive activity of the β-catenin-Tcf4 transcription complex. The proto-oncogene c-MYC has been identified as a target of the Wnt pathway in colorectal cancer cells in vitro, in normal crypts in vivo’ and in intestinal epithelial cells acutely transformed on in vivo deletion of the APC gene; The role of Myc in the intestine after Ape loss has been studied , after deleting both Apc and Myc in the adult murine small intestine. Loss of Myc reversed the phenotypes of perturbed differentiation, migration, proliferation and apoptosis, which occur on deletion of Ape Myc is required for the majority of Wnt target gene activation following Apc loss. These data establish Myc as the critical mediator of the early stages of neoplasia following Ape loss.
This may appear obscure to Nutritionists.
If we are to break away from repeated mantras that certain food items are involved in the ain science will be seen as poking sticks down a rabbit hole and hoping for something to turn up.

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Photosynthesis - the light of life

Evidence for wavelike energy transfer through quantum coherence in photosynthetic systems
Engel and colleagues
Nature vol 446, 12th April 2007
This summary is taken from Nature. Whilst the detailed chemistry is unlikely to appeal to most Nutritionists this is a fundamentally important process for life . It is therefore worth having a look at and even 10% uptake is valuable. Nutrition is a science and also we should be educated .
If nothing else knowing of the Fenna-Matthews-Olson (FMO) bacteriochlorophyll complex, will give you an edge in any Pub quiz.
Photo synthetic complexes are exquisitely tuned to capture solar light efficiently, and then transmit the excitation energy to reaction centres, where long term energy storage is initiated. The energy transfer mechanism is often described by semi classical models that invoke ‘hopping’ of excited-state populations along discrete energy levels’”. Two-dimensional Fourier transform electronic spectroscopy”’ has mapped” these energy levels and their coupling in the Fenna-
Matthews-Olson (FMO) bacteriochlorophyll complex, which is found in green sulphur bacteria and acts as an energy ‘wire’ connecting a large peripheral light-harvesting antenna, the chlorosome, to the reaction centre. . The spectroscope data clearly document the dependence of the dominant energy transport pathways on the spatial properties of the excited-state wavefunctions of the whole bacteriochlorophyll complex. But the intricate dynamics of quantum coherence, which has no classical analogue, was largely neglected in the analyses—even though electronic energy transfer involving oscillatory populations of donors and acceptors was first discussed more than 70 years ago, and electronic quantum beats arising from quantum coherence in photo synthetic complexes have been predicted and indirectly observed. Here we extend previous two-dimensional electronic spectroscopy investigations of the FMO bacteriochlorophyll complex, and obtain direct evidence for remarkably long-lived electronic quantum coherence playing an important part in energy transfer processes within this system. The quantum coherence manifests itself in characteristic, directly observable quantum beating signals among the excitons within the Chlorobium tepidum FMO complex at 77 K. This wavelike characteristic of the energy transfer within the photo synthetic complex can explain its extreme efficiency, in that it allows the complexes to sample vast areas of phase space to find the most efficient path..
The system is essentially involved in a process wherein many senses are sensed at the same time and allowing the most effective transfer of energy to the correct locus.
This mechanism contrasts with a semi classical ‘hopping’ mechanism through which the excitation movesstepwise from exciton state to exciton state, dissipating energy at each step, which would be similar to a classical search where only one state can be occupied at any one time. Such a mechanism also raises the possibility of non-local events.
The FMO light-harvesting complex provides an opportunity to apply more complete energy transfer theories that invoke non-markovian dynamics and include coherence transfer. Such theories need to include wavelike energy motion owing to long-lived coherence terms, alongside the population transfer included in current models. Further, the observed preservation of coherence in this photosynthetic system requires us to redefine our description of the role of electron-phonon interactions within photosynthetic proteins. In particular, the protein may not only enforce the structure that gives rise to the couplings, but also modulate those couplings with motions of charged residues and changing local dielectric environments, which will change exciton energies and promote coherence transfer.

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Saturday, April 07, 2007

Global warming more gloom

Global warming is constantly in the aware persons mind. As the spring comes with unusual warmth there will be many for whom the warmth means no rain, no water and all the consequences. The rich will for a while get richer and the poor well. let them get on with it.
The immediately recent conference in Brussels has gone through the science and politics of global warming. It may be that there are two things happening, a natural fluctuation in the solar protective blanket accentuated by human activity. The natural protective adjustments of nature cannot operate as has happened in the past because mankind has so altered our environment that it is not easy.
Whilst scientists point out the dangers of global warming , Science must take full responsibility. For it is science which has given us the where withal to indulge in global warming. We scientists are the cause.
The politicians represent the people and have to adjust to our changes. Often very appealing.
As the drought extends there will be large sale famines and water shortages. There will be massive movement or attempts at massive movements from the southern continents, Asia, Africa and South America. Quit a prospect.

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Thursday, April 05, 2007

Glycaemic index and life.

The low glycaemic index diet Ludwig: Lancet 2007, vol 369, March 17, 890-892

David Ludwig has written a thought provoking article on the glycaemic index(GI) This concept has been around for more than 20 years. The argument for this measure is that it is a guide allowing the classification of health providing properties of carbohydrate meals. Eating simple sugars which are rapidly absorbed is a challenge to the body hormonal system.
GI is determined by measuring the 2 hour incremental area under the glucose curve after taking 50 g of carbohydrate and comparing this with a white bread or glucose load. The higher the GI the greater the potential hormonal challenge to glucose homeostasis. . Glycaemic load (CL) is the average GI multiplied by the carbohydrate amount.
It is also claimed that in times gone past that we ate a diet that was characterised by a lowGI. It is a absolute necessity for any theory that the central element is unchallengeable by measurement. Who knows how our primeval ancestors ate. Feast and famine, hunting ,gathering , good weather ,bad weather, fierce carnivores hunting for the same food .No shop until you drop but hunt and gather before you drop. Early death from all manner of pestilences.
The bolus of food can be seen as a sponge. The glycaemic curve will be dependent upon
time of chewing .
length of time spent ingesting the food or drink e.g. sipping. A simple experiment is sipping a glass of wine or gulping it down.
Eating communally is important. In contrast to the snatched meal.
gastric emptying time. This is determined by the chemistry of the food ingested e.g. fat has the greatest retarding effect. So a piece of white bread coated with butter and a protein paste will have a lower GI than white bread on its own
How the ingested food was prepared .
Each of us has two experiments going. One’s own eating habits and that of people we are advising. What do we really enjoy?
Perhaps GI should only be part of a dietary regime. That the forbidden treats be eaten slowly and in discrete amounts. Food is a real treat in life. There is such a contrast between the snatched sandwich and a couple of pints in a Pub before an important game and the slow meal eaten amongst family and friends for Sunday lunch. Both are fun and should live together. A mix is all important.

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Wednesday, April 04, 2007

Zinc supplementation and child mortality in Zanzibar

Zinc and child mortality.

Pneumonia, diarrhoea, and malaria account for 45% of the 10-6 million yearly deaths of children younger than 5 years despite some success with preventive and therapeutic interventions. 2-6 million of these deaths take place in Africa, including 90% of the 0-8 million worldwide childhood malaria deaths every year. Finding cheap methods for reducing such mortality, would help countries achieve the Millennium Development Goal of two-thirds reduction in child mortality. The cost of this awful mortality rate does not also take into account the danger to the mothers of these children in the pregnancy where there is also a significant death rate and morbidity e.g. fistula.
Deficiency of a few essential micronutrients is recognised to greatly increase the risk of morbidity and mortality from infectious diseases in developing countries. Evidence for zinc as one such important micronutrient has emerged; in addition to data linking zinc deficiency to growth retardation and impairment of immune function, zinc supplementation has shown significant reduction in rates and severity of diarrhoea and pneumonia, (the two main causes of under-5 mortality). Three small trials in-Asian populations without malaria showed that zinc supplementation significantly reduced child mortality. Evidence for the benefit of zinc supplementation on malaria morbidity has been inconsistent. Sazawal and his colleagues
(Lancet , 369, 927-933) undertook a community-based trial to assess the effect of zinc supplementation on mortality in children aged 1-48 months in Pemba, Zanzibar, a place with a high-frequency of malaria transmission.
There were 42,546 children in the study, and the result was a 7% reduction in the relative risk associated with zinc supplementation.
Such studies are fraught with problems ( Bhatnagar in Lancet 2007, 369, 885-6). The dosage of zinc varies, the type of zinc preparation and bioavailability varies, compliance must be a problem from small to large studies and the study populations. At least in this study there was an improvement , in some vitamin / cancer studies the mortality has risen.
At the end of this stage of the economy in these countries, zinc ,and oral rehydration fluids possibly vitamin A availability are important community strategies to reduce the death toll.
An adequate clean diet and fluid is the real end objective.

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Tuesday, April 03, 2007

piles of oranges

Everyone is familiar with the stacking of oranges in a pyramid on Market stalls and in green grocery shops.
The simplicity and familiarity of this hides an interesting question about stacking theory.
In two dimensions, if one wants to place the maximum number of circles e.g. coins of the same denomination around a central circle or coin, the maximum number is always six, the kissing number.. That is a hexagonal lattice.
Oranges, when stacked in a pyramid have a kissing number of 12, which is the three dimensional extension of this system. Each orange enclosed inside this stack is in contact with 12 neighbours. The ranking of kissing numbers for spaces and dimensions is 1, 2, 3, 8 and 24.
All to do with sphere packing and binary codes.
And what has this to do with nutrition. Well oranges are said to be healthy foods to eat. So what better object to study sphere packing and binary codes. Which all began with Kepler’s book in 1611 on why a snow drop has a 6 membered symmetry.
Stewart, (2003) Nature 424, 895-6

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life and death in cells, glycolysis and apoptosis

All organisms reqire energy for their activity.
Central to this is glycolysis . Glycolysis is the pathway in which glucose is metabolised before splitting into two interconvertible 3-carbon molecules . These reactions take place in the cell cytoplasm. The first three steps involve reactions which lead to a doubly phosphorylated fructose derivative, Glucose 1-phosphate, glucose 6-phosphate and fructose 6-phosphate readily interconvert and thereby form a single metabolic pool. Glucose 1-phosphate is the first product in the catabolism of storage polysaccharides, e.g. starch, Glucose 6-phosphate is the first hexose phosphate generated when free glucose is metabolised and fructose 6-phosphate is the first hexose phosphate formed when the carbohydrate is derived from non carbohydrate precursors.
Glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P) readily interchange through the action of the enzyme glucose phosphate isomerase. The available amount is dependent upon the phosphorolysis of storage polysaccharides, yielding glucose 1-phosphate, by the phosphorylation of glucose yielding G6P or by gluconeogenesis of F6P. The subsequent catabolic steps are:
glycolysis with F6P as the starting point
the pentose phosphate pathway which uses G6P.
Alternatively G6P and F6P can be converted into storage polysaccharides with G6P acting as the starting point. G6P can also be hydrolysed to yield free glucose to be transported in the blood to peripheral tissues.
Cell death apoptosis , Apoptosis is a coordinated, programmed, genetically regulated form of cell death. A multicellular organism must sustain equal rates of cell generation and cell death to maintain a constant size. Senescent, damaged or abnormal cells that could interfere with organ function must be removed. Physiological cell death is not a random process. Apoptosis is important in organ atrophy and during disease with a decrease in cell numbers. Apoptosis is a rapid process and is directed towards scattered individual cells rather than all the cells in a particular area. It occurs during embryogenesis in the process of tissue turnover and after withdrawal of a trophic hormone from its target tissue. Apoptosis is a mechanism whereby organs and digits in the hand and foot are sculptured out in the evolving foetus.
In the adult some 10 billion cells die each day to balance new production. An example of apoptosis in the adult is a shedding of intestinal cells. Apoptosis may be important in autoimmune disease, degenerative diseases and ageing. The decline in body cell mass with age is probably controlled genetically, as it is related to life span.
Early in apoptosis the distinct morphological features include compaction of chromatin against the nuclear membrane, cell shrinkage and preservation of organelles, detachment from surrounding cells and nuclear and cytoplasmic budding to form membrane-bound fragments (apoptotic bodies). These are rapidly removed by adjacent parenchymal cells or macrophages. An enzyme system caspases dismantle the cell from within in an orderly manner. These are triggered by the release of cytochrome c. Proteins of the BCL-2 family are key regulators of apoptosis , either stimulating or preventing apoptosis. . A pro-apoptotic BCL-2 protein is BAD, which when phosphorylated is sequestrated into inactive complexes and no longer cause cell death.
Mitochondria have a central role in both glycolysis and apoptosis BAD may be an important protein in life and death of cells. BAD is also present in large protein complexes which regulate BAD phosphorylation eg protein kinase A, protein phosphatase 1 and surprisingly glucokinase. Central to glycolysis.
There are other close links between apoptosis and glycolysis by control mechanisms e.g. growth factors. BAD may have an influence on metabolism. Glucose mediated phosphorylation of BAD might increase glycolysis and prevent cell death.
Downward (2003) Nature , 424, 896-7

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Sunday, April 01, 2007

global change, UN report

Global Warming.
The International Panel on Climate Change and the United Nations will publish predictions as to the effects of global warming in this coming wee. It is predicted that the earth’s temperature will increase by 3 degrees centigrade by the end of this century. What happens after this in subsequent centuries is not clear.
The Financial Times of March 31 2007, p9reports that the warning will include
1. North America, Northern Europe and Russia milder climates will benefit tourism, allow farmers to grow wider crop variety with increased crops and that melting ice will allow mineral and oil extraction form the Arctic. Heat will damage transport infrastructure ( e.g. road surfaces may melt ), housing structure have to change to cope with heat and plant and animal pests will spread North. Grapes will grow in northern countries e.g. Scotland.
2. Southern Europe Agricultural yields will fall , droughts will be widespread
3. East Asia. Increased cyclone activity and higher storm intensity.
4. Southern USA and Caribbean . Increased hurricane activity, lower agricultural yields and worsening droughts.
5. Africa. Further spread of malaria and dengue fever epidemics, reduced crops, droughts , mass migration and probably conflict.
6. Southern Asia. Floods as the Antarctic glaciers melt , spread of diseases in man , animals and plants.
Australia. Droughts, spread of deserts and loss of agricultural land.
Oceans. Higher content of CO2 and acidification of the water with consequences for fish and plant life.

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grape coloration, red or white

White and red grapes

The wild grape is red. During the domestication of the grape a white cultivar developed. This may have occurred 3,000 or so years age. In 2005 Japanese scientists showed that this colour change occurred because of a mutation in the VvMYBA1 gene. This difference is consistent over the whole grape range, between red and white grapes. The gene controls the production of the red colour anthocyanin. This colour is also found in apples, strawberries, purple cabbage and blueberries
More recently Mandy Walker and her colleagues in the Commonwealth Research Organisation in Australia showed two genes along side each other which control anthocyanin production. Both must be mutated in the white grape.
This suggests that all the white grapes have a common ancestor. Seeds of white grapes have been fond in the tomb of the Egyptian King Tutankamen ( 1322 BC ). So the mutation antedates this.
This was reviewed by Stephen Pincock in FT magazine March 3, 2007, p 11

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