Sheila Bingham

Sheila Bingham has died ( 1947-2009) . She was based in Cambridge and her contributions to sensible Nutrition science were enormous. If you go into Pub Med and look at her papers there are always valuable insights with each and every one of her papers.
She was also a very nice person. A splendid team player, which is not a common gift.
A loss.

DNA-protein binding

The genetic information embodied in DNA must be decoded at the right time and in the right type of cell. To achieve this, proteins that control such processes have to bind to specific places in the genome. How a protein finds the correct spot to bind to among all the possible sites (3 billion base pairs in the human genome, for example) has been the preoccupation of molecular and structural biologists for decades.
A protein could recognize its binding site in the genome by somehow 'reading' the DNA and this is the case from studying structures of protein- DNA complexes. The DNA double helix has two grooves, a major and a minor one, that wind around the central axis of the molecule, and reading is achieved using hydrogen bonds that form between protein side chains and the edges of the DNA nucleotides that are exposed in the major groove. But unlike the genetic code, a simple code for protein recognition of DNA has not emerged despite years of effort.
DNA is a molecule with a three-dimensional shape that is not perfectly uniform. Rohs et al. in Nature (2009 p 1248-53 vol 461 1248-1253) show that one structural feature of DNA, the shape of its minor groove, can be exploited by proteins for specific recognition.
A particular sequence of nucleotides presents a unique array of hydrogen-bond donors and acceptors in the major groove, providing a clear mechanism for reading that sequence,
The width of the minor groove varies depending on which nucleotides are present in a segment of DNA. The width of the minor groove has a physical consequence that goes beyond the merely structural, stemming from the charged groups (phosphates) that are arrayed along the outer edge of the DNA backbone, one per nucleotide . Where the minor groove is narrow, the electric-field lines due to the negatively charged phosphates are focused into the groove, leading to an enhanced negative electrostatic potential in that segment of the double helix.
Rohs and colleagues have looked at the databases of three-dimensional structures of protein-DNA complexes and found many examples of proteins that use amino acids containing positively charged side chains, principally arginines, to read the electrostatic potential of the minor groove. Where the groove width and electrostatic potential are optimal, an arginine side chain of a DNA-binding protein is often seen to sit in the minor SI groove

The shape of the minor groove of DNA can direct the binding of proteins to specific sites.
Negatively charged phosphate groups are arrayed along the outer edge of the D A major and minor grooves that spiral around the axis of the double helix. The width of the minor groove varies depending on the sequence of nucleotides. This variation leads to differences in the distance between phosphates across the groove, which in turn lead to variation in the negative electrostatic potential along the minor groove.
Tullius 2009 DNA binding shapes up Nature vol 461 pp 1225-6

history of alcohol production

This book by McGovern on a history of alcohol making suggested that the desire for alcohol is innate in human beings. The “ uniquely human traits “ of self-consciousness, innovation , the arts and religion have been encouraged by the consumption of alcohol
Alcohol has been made of thousands of #years.
Evidence of alcohol being made has been fond in the Zagros Mountains in Western Iran.
An alcoholic drink from fermented rice, honey and hawthorn fruit was produced in China inn 7000 BC.
McGoern PE 2009 Uncorking the past: the quest for wine, beer and other alcoholic beverages. University of California Press

Nutrition or sportsman

FOOD & Drink for Footballers and other Sportsmen

WATER is important to keep you hydrated.

Drink water before the game and at half time. Energy drinks are ok but water is vital

PROTEIN is important, if possible, every day.

Meat, chicken, eggs, bread, beans.

This helps build muscles.

VITAMINS

Fruit, vegetables & fresh fruit juices, the famous five (a day) are still as good as ever.

ENERGY

You need energy stored in the body to last the full game.
Energy comes from sugar. You can get different sugars from different foods

Quick acting energy comes from ordinary sugar

Found in sugary drinks, sweets and chocolate bars.

These are good to eat at half time, but can damage your teeth if too much is eaten.


Slow acting energy comes from starchy foods (stores energy for long term fitness)

Found in bread, pasta, potatoes, rice, breakfast cereals, beans and bananas.

It is good to eat some slow acting energy food twice on the day of the game

In the morning before the game

And later on in the day

Try to eat 2 of these foods every day


These foods and drinks could make you a better player who is energetic all through the game, and help you be a winner!!!



Along with exercise, food and drink are vital for young football winners!

DNA damage and repair

This is a fascinating review by Jackson and Bartekon the DNA-damage response in human biology and disease in Nature .
Tens of thousands of DNA in each of the 1013 cells in the human body is damaged each day. These lesions can block genome replication and transcription, and if they are not repaired or are repaired incorrectly, they lead to mutations or wider-scale genome aberrations that threaten cell or organism viability. Some DNA aberrations arise through physiological processes, such as DNA mismatches occasionally introduced during DNA replication and DNA strand breaks caused by abortive topoisomerase I and topoisomerase II activity. In addition, hydrolytic reactions and non-enzymatic methylations generate thousands of DNA-base lesions per cell per day. DNA damage is also produced by reactiveoxygen compounds arising as by-products from oxidative respiration or through redox-cycling events involving environmental toxic agents and Fenton reactions mediated by heavy metals. Reactive oxygen and nitrogen compounds are also produced by macrophages and neutrophils at sites of inflammation and infections. Such chemicals can attack DNA, leading to adducts that impair base pairing and/or block DNA replication and transcription, base loss, or DNA single-strand breaks. Furthermore, when two single-strand breaks s arise in close proximity, or when the DNA-replication apparatus encounters a single-strand breaks or certain other lesions, double-strand breaks single-strand breaks are formed. Although double-strand breaks do not occur as frequently as the other lesions listed above, they are difficult to repair and extremely toxic.
The most pervasive environmental DNA-damaging agent is ultraviolet light. Although the ozone layer absorbs the most dangerous part of the solar ultraviolet spectrum (ultraviolet C), residual ultraviolet A and ultraviolet B in strong sunlight can induce -100,000 lesions per exposed cell per hour. Ionizing radiation also generates various forms of DNA damage, the most toxic of these being double-strand breaks. Some ionizing radiation results from radioactive decay of naturally occurring radioactive compounds. For example, uranium decay produces radioactive radon gas that accumulates in some homes and contributes to lung-cancer incidence. Exposure to natural or manmade radioisotopes also occurs during cancer radiotherapy, whereas the radioactive compounds iodine-131 and technetium-99m are exploited to diagnose and treat benign and malignant thyroid diseases. Lessons about the health consequences of excessive radiation exposure are provided by the aftermaths of the Chernobyl nuclear-reactor disaster and nuclear detonations over Japan in the Second World War.
Today, probably the most prevalent environmental cancer-causing chemicals are those produced by tobacco products, which trigger various cancers, most notably those of the lung, oral cavity and adjacent tissues. Cancer-causing DNA-damaging chemicals can also contaminate foods, such as aflatoxins found in contaminated peanuts and heterocyclic amines in over-cooked meats. DNA-damaging chemicals have also been used in warfare, and on a more positive note, are widely used to treat cancers and ailments such as psoriasis.
They describe how DNA lesions are dealt with at the molecular level. The presence of a lesion in the DNA, which has consequences for replication is recognised by various sensor proteins. These proteins initiate many cellular processes, with biological significance which have roles in preventing human diseases. These include DNA repair pathways, DNA damage signalling and cell cycle checkpoints, a DNA damage response system.
Jackson and Bartek 2009 The DNA-damage response in human biology and disease Nature vol 461 pp 1071-78

genes and potential cancer therapy

RAS is one of the most commonly mutated gene families in human cancers - one of its three members (KRAS, HRAS and NRAS) is mutated in about 20% of human tumours. Attempts to target mutant RAS proteins directly with small-molecule inhibitors have so far proved unsuccessful, so there has been considerable interest in finding signalling pathways that function downstream of RAS and whose blockade might be selectively toxic to tumour cells. Two papers in Nature 5th November 2009 provide evidence that targeting one such pathway, the NF- KB signalling pathway, may be an effective approach to treat RAS-mutant tumours such as lung cancers. Barbie et al.' (page 108) identify a component of the NF-KB pathway as a potential target in RAS-mutant cancer cells, and Meylan et al' (page 104) show that inhibition of NF-KB signalling impairs tumour formation in a mouse model ofRAS-induced lung cancer. The NF-KB transcriptional program control is a multitude of cell functions, most notably the regulation of cell death and inflammation
The use of the RNA-interference technique to selectively inhibit gene expression, together with knowledge of the full sequence of the human genome, has made possible large-scale functional genomic screens. In these, each gene in the genome (or at least a significant proportion of genes) is silenced one by one, and the effect on cell function is assayed. This approach has recently been used to investigate which genes, when silenced, kill cells bearing mutant RAS but not cells that lack this mutation so-called synthetic lethal interactions. Barbie et al' looked for synthetic lethal interactions in a panel of cell lines, some of which had activating mutations in KRAS. The authors inhibited genes thought to be important for the development of cancer and identified several genes whose reduced activity seemed to selectively kill the RAS-mutant cells. After KRAS itself, silencing the gene TBK1, an upstream regulator of the NF-KB pathway, was most effective for selectively killing RAS-mutant cells. TBK1 is thought to activate NF-KB by phosphorylating IKB, an F-KB inhibitor. It also activates other transcription factors involved in inflammatory responses, such as IRF3 and IRF7 .
Downward 2009 A tumour gene’s fatal flaws Nature vol 462 pp 44-45

n-3 polyunsaturated fatty acids and fat tissue

Adipose tissue has a key role in the development of metabolic syndrome which includes obesity, type 2 diabetes, dyslipidaemia, hypertension and other disorders. Systemic insulin resistance represents a major factor contributing to the development of metabolic syndrome in obesity. The resistance is precipitated by impaired adipose tissue glucose and lipid metabolism, linked to a low-grade inflammation of adipose. tissue and secretion of pro-inflammatory adipokines. Development of metabolic syndrome could be delayed by lifestyle modifications, while both dietary and pharmacological interventions are required for the successful therapy of metabolic syndrome . The n-3 long-chain polyunsaturated fatty acids , EPA and DHA, which are abundant in marine fish, act as hypolipidaemic factors, reduce cardiac events and decrease the progression of atherosclerosis. Thus, n-3 long chain polyunsaturated fatty acids represent healthy constituents of diets for patients with metabolic syndrome . In rodents n-3 long chain polyunsaturated fatty acids prevent the development of obesity and impaired glucose tolerance. The effects of n-3 long chain polyunsaturated fatty acids are mediated transcriptionally by AMP-activated protein kinase and by other mechanisms. n-3 long chain polyunsaturated fatty acids activate a metabolic switch toward lipid catabolism and suppression of lipogenesis, i.e. in the liver, adipose tissue and small intestine. This metabolic switch improves dyslipidaemia and reduces ectopic deposition of lipids, resulting in improved insulin signalling. Despite a relatively low accumulation of n-3 long chain polyunsaturated fatty acids in adipose tissue lipids, adipose tissue is specifically linked to the beneficial effects of n-3 long chain polyunsaturated fatty acids, as indicated by (1) the prevention of adipose tissue hyperplasia and hypertrophy, (2) the induction of mitochondrial biogenesis in adipocytes, (3) the induction of adiponectin and (4) the amelioration of adipose tissue inflammation by n-3 long chain polyunsaturated fatty acids.
Kopecky et al 2009 n-3 PUFA : bioavailability and modulation of adipose tissue function Proceedings of the Nutrition Society vol 68 361-369
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mitochondrial bar code

Mitochondria, the cell's energy producers, are descended from free-living bacteria that took up residence within other cells some 2 billion years ago. They have a modest genetic size being only 37 genes in vertebrates, compared with more than 20,000 in a nucleus.
Yet within this little genome, researchers have identified a 64S-nucleotide stretch as the ultimate identifier of species, dubbed the DNA bar code. The sequence can distinguish between closely related species such as humans and chimps and even classify new species from identical-looking ones, such as the blue-flasher butterfly (Astraptes fulgerator), which has since been divided into ten separate species, verified by the habitats, lifestyles and diets of their caterpillars. ,
The DNA bar code has been both praised and attacked for its simplicity.
Lane 2009 On the origins of bar codes Nature vol 462 pp272-3