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p53, viral inactivation and cancer

noreply@blogger.com (Martin Eastwood) — Wed, 08 Sep 2010 05:31:34 PDT

It is a self evidence that where ever a phenomenon in biology, there is always a claim that nutrition has a place in the process. Maybe. This might be true.
Cancer is an omnipresent candidate for nutritional cause and cure. This paper is a wake up call that there are other more scientifically based possible causes of cancer.
The transcription factor p53 (also known as TP53) guards against tumour and virus replication and is inactivated in cancers. p53-activated transcription of target genes is thought to be synonymous with the stabilization of p53 in response to oncogenes and DNA damage. During adenovirus replication, the degradation of p53 by E1B-55k is considered essential for p53 inactivation, and is the basis for p53-selective viral cancer therapies. This paper shows a dominant epigenetic mechanism that silences p53-activated transcription, irrespective of p53 phosphorylation and stabilization. An adenoviral protein, E4-0RF3, inactivates p53 independently of E1B-55k by forming a nuclear structure that induces H3K9me3 heterochromatin formation at p53 target promoters, preventing p53-DNA binding. This suppressive nuclear web is highly selective in silencing p53 promoters and operates in the backdrop of global transcriptional changes that oncogenic replication. These findings are important for understanding how high levels of wild-type p53 might also be inactivated in cancer as well as the mechanisms that induce aberrant epigenetic silencing of tumour-suppressor loci. This study changes the longstanding definition of how p53 is inactivated in adenovirus infection and provides key insights that could enable the development of true p53-selective oncolytic viral therapies.
Soriaet al 2010 Heterochromatin silencing of pS3 target genes by a small viral protein. Nature vol 466, pp 1076-1081

drug treatment of excess weight

noreply@blogger.com (Martin Eastwood) — Fri, 27 Aug 2010 07:08:20 PDT

Few safe and effective drug treatments are available. A combination treatment with sustained-release naltrexone and bupropion has been developed to produce complementary actions in CNS pathways regulating bodyweight. Two key systems are identified, the hypothalamic melanocortin sytem which integrates input related to energy balance and produces anorexigenic signalling and mesolimbic reward system which modulates reward value and goal orientated behaviour.
The Contrave Obesity Research I (COR-I) study assessed the effect of such treatment on bodyweight in overweight and obese participants.
1742 men and women aged 18-65 years who had a body-mass index (BMI) of 30-45 kg/m2 and uncomplicated obesity or BMI 27-45 kg/m2 with dyslipidaemia or hypertension were recruited to this randomised, double-blind, placebo-controlled, phase 3 trial.
Participants were prescribed mild hypo caloric diet and exercise and were randomly assigned in a 1:1:1 ratio to receive sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB32), sustained-release naltrexone 16 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NBI6), or matching placebo twice a day, given orally for 56 weeks. The trial included a 3-week dose escalation.
The endpoints at 56 weeks were percentage change in bodyweight and proportion of participants who achieved a decrease in bodyweight of 5% or more.
Pparticipants were enrolled and randomised to double-blind treatment (naltrexone 32 mg plus bupropion, n=583; naltrexone 16 mg plus bupropion, and completed 56 weeks of treatment Mean change in bodyweight was -1• 3% in the placebo group, -6 •1% in the naltrexone 32 mg plus bupropion group and -5•0% (0•3) in the naltrexone 16 mg plus bupropion group
84 (16%) participants assigned to placebo had a decrease in bodyweight of 5% or more compared with 226 (48%) assigned to naltrexone 32 mg plus bupropion (pThe report concluded that there was some place for such treatment.

Greenway et al 2010 Effect of naltrexone plus bupropion on weight loss in
overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial The Lancet vol 376 595-605

bones and metabolism

noreply@blogger.com (Martin Eastwood) — Wed, 25 Aug 2010 02:12:16 PDT

Most scientists believe the function of the bone is limited to support and mineral exchange.
A stimulating article in Nature discusses the possibility that bone remodelling be linked to metabolism. This makes real sense as metabolism is interconnected and a stand alone system cannot be efficient.
The article discusses the work generated by Karsenty and Ducy on this topic.
Bone remodelling includes both bone building by osteoblasts and removal by ostosclasts. This is an energy intensive process and interacts with metabolism in a number of ways. The hormone Leptin which is secreted by fat cells and affects appetite inhibits osteoblast formation and osteocalcin, a bone related protein production. Osteoblasts increase concentrations of inactive osteocalcin.
Bone removal activates osteocalcin. Osteocalcin stimulates pancreatic β-cells to produce insulin. And straight into metabolism.
Katsnelson 2010 The bones of contention. Nature vol 466 pp 914-915

p53 and metabolism

noreply@blogger.com (Martin Eastwood) — Tue, 24 Aug 2010 23:17:52 PDT

The tumour suppressor gene p53 is important in halting the cycle and death when there is DNA damage.
P53 also has a role in cellular metabolism. The inactivation of p53 is common in tumours . P53 contributes to a shift from oxidative phosphorylation to glycolysis. This shift originally described by Warburg is a feature of tumour cells.
GLS2 an enzyme involved in oxidative phosphorylation is regulated by p53 under stressed and non stressed conditions. GLS2 increases the respiration rate in mitochondria with resultant increased production of ATP.
Meline 2010 Journal Club . Nature vol 466 p 905

anxiety and the brain

noreply@blogger.com (Martin Eastwood) — Mon, 16 Aug 2010 23:50:09 PDT

Some people are naturally more anxious than others.
How anxiously we react to threat or adversity is part of our personality. This characteristic is called trait anxiety, and those with high trait anxiety are more prone to mental disorders such as depression, substance abuse and psychosis. Trait anxiety is heritable, with genes explaining much of the variability between individuals.
Oler et al have investigated genetic effects on the activity of brain regions that mediate trait anxiety.
The subjects of this study were rhesus monkeys, from several generations of a single-family pedigree - at an average age corresponding to that of humans just before puberty. The authors exposed the animals to a human intruder, a social-threat procedure that reveals an anxiety trait. They found, by examining both blood levels of the stress hormone cortisol and behaviours such as 'freezing: that some monkeys reacted with high anxiety, and others with less.
Oler et al. also measured metabolic activity in the brain by injecting the monkeys with 18FDG, a radioactive analogue of glucose that is taken up and trapped in nerve cells according to their activity at the time of exposure to the social threat. The authors then anaesthetized the monkeys in order to image, using positron emission tomography, a 'snapshot' of regional brain metabolism during the preceding stress procedure.
The results indicate that, in anxious monkeys, brain activity is higher in a variety of areas, but most prominently in two key signalling structures for negative emotion, the amygdala and the anterior hippocampus. Activity in these two structures explained a sizeable proportion of the variance in anxiety behaviour from monkey to monkey
Much research in anxiety has focused on the amygdala , which signals environmental danger and triggers 'fight-or-flight' responses. But extensive evidence also links the anterior hippo¬campus, an essential structure for 'declarative' memory - to anxious behaviour and trait anxiety. Furthermore, there are strong interactions between the amygdala and hippocampus, which mediate emotional memory.
Activity in the anterior hippocampus is under greater genetic influence but found no significant heritability in the amygdala.

Oler et al 2010 Amygdala and hippocampal substrates of anxious temperament differ in their heritability vol 466 pp 864-868.
Meyer-Lindenberg 2010 Genes and the anxious brain Nature vol 466 pp827-8

paternal and maternal genes

noreply@blogger.com (Martin Eastwood) — Mon, 16 Aug 2010 23:24:40 PDT

Some genes exclusively express only their maternal or paternal copy.
Mammals inherit one copy (allele) of each gene from their mother and another copy from their father. Yet for many genes, only one of these alleles is always expressed in a cell. The choice of which allele is expressed is random in some cell types - notably those of the olfac¬tory and immune systems; for others, such as those of the developing placenta and brain, certain genes are 'imprinted". The hallmark of imprinted genes is that some are expressed only when inherited from the mother and others only when inherited from the father.
Imprinted genes were thought to be fewer than 100 in number.
Studies published in the Journal Science by Gregg and colleagues identify 1,308 candidate imprinted genomic regions in the mouse brain, encompassing 824 annotated genes as well as the entire X chromosome.
It has already been shown that, in the mouse placenta, the X chromosome is imprinted, with genes from the maternal X being exclusively expressed, thereby avoiding immunological rejection of foreign fetal proteins that might be encoded by the paternal X chromosome",

Many of the genes on the X chromosome are also expressed in the brain. In males (XY), the single X copy always originate from the mother, but in females ( XX) either the maternal or the paternal copy of the X chromosome is inactivated early in embryonic development, and this occurs at random. Gregg et al report preferential expression of the maternal X chromosome in two brain regions. Compared with the paternal X, the expression of the maternal X chromosome was 11 % higher in glutamate-secreting neurons of the cortex, and 19% higher in the preoptic region of the basal forebrain.
In general, the expression of imprinted genes is exclusively either maternal or pater¬nal, with loss of exclusivity usually leading to expression of both alleles. This suggests that the biased gene expression described by Gregg et al. may be due to selection of cells express¬ing the maternal X chromosome, rather than imprinting. DNA replication errors increase with the number of cell divisions, which are an order of magnitude higher in the production of sperm than female oocytes
Keverne 2010 A mine of imprinted genes Nature vol 466 pp 823-4

ocean oxygen concentration

noreply@blogger.com (Martin Eastwood) — Mon, 16 Aug 2010 09:15:31 PDT

In July 2002, scientists with the Oregon Department of Fish and Wild¬life found unusual numbers of bottom¬feeding sculpin lying lifeless on the ocean floor, which would normally be teeming with life. Crabs were also dying, and they washed up onto some beaches in large numbers.
Ocean surface waters normally contain 5-8 millilitres of oxygen per litre of water, which declines rapidly with depth. At a depth of 50 metres the inner coastal waters off Oregon were hypoxic - oxygen levels there were lower than 1.43 millilitres per litre, so low that fish can't survive,
Many regions of the world have hypoxic coastal waters, usually caused by agricul¬tural fertilizers leaking into the ocean. The excess nutrients fuel plankton blooms, which consume oxygen.
Every summer since then, much of the oxygen has disappeared from a large patch of inner continental-shelf waters. In the most extreme case, in 2006, the waters lost all detectable oxygen for four weeks. Starfish and mussels died, and rockfish and other mobile fish fled the hypoxic zone, which grew to 3,000 square kilometres .
The phenomenon has worried the fishing industry in Oregon, which brings in hun¬dreds of millions of dollars each year and
This is phenomenon is being pound elsewhere in the world. It is not clear if this is secondary to Global Warming. But warmer water temperatures may be important contributory factors.
Usually in the spring , occasional periods of Northerly winds blow surface water off shore, allowing cool water, rich in nutrients but poor in oxygen to rise form deeper offshore layers.
Gewin 2010 Dead in the water Nature vol 104 pp 812-3

oat bran molecular weight and cholesterol lowering effect

noreply@blogger.com (Martin Eastwood) — Mon, 16 Aug 2010 08:55:19 PDT

The physical form of food may well be a factor in its metabolism in the gastro intestinal tract. In this study, the authors looked at the cholesterol-lowering effects of different oat bran (oat bran) preparations, differing and their peak molecular weight (MWp) of β-glucans (2348,1311,241,56, 2l or < l0kDa), in mice. The diets were designed to be atherogenic (0•8 % cholesterol and O•l % cholic acid), and they reflected the Western diet pattern (41 % energy fat). All oat bran preparations that were investigated significantly reduced plasma cholesterol when compared with a cellulose-containing control diet, regardless of the molecular weight of β-glucan. Moreover, the difference in viscous properties between the processed oat bran (from 0•l1 to 17•7I1g) did not appear to play a major role in the cholesterol-lowering properties.
There was no correlation between the molecular weight of β-g1ucan and the amount of propionic acid formed in caecum.There was a significant correlation between the ratio of (propionic acid + butyric acid)/acetic acid and the MWp of β -glucans: the ratio increased with increasing molecular weight. The results of the present study suggest that the molecular weights and viscous properties of β-glucan in oat products may not be crucial parameters for their cholesterol-lowering effects.
Immerstrand et al 2010 Effects of oat bran, processed to different molecular weights of β -glucan, on plasma lipids and caecal formation of SCFA in mice Brit Journal Nutrition vol 104 364-373

omega 3 fatty acids and the heart

noreply@blogger.com (Martin Eastwood) — Mon, 16 Aug 2010 07:01:11 PDT

Much evidence shows that the marine omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid have beneficial effects in various cardiac disorders, and their use is recommended in guidelines for management of patients after myocardial infarction. Questions have been raised about their usefulness alongside optimum medical therapies with agents proven to reduce risk of cardiac events in high-risk patients. Additionally, there is some evidence for a possible pro-arrhythmic effect in subsets of cardiac patients. Some uncertainly exists about the optimum dose needed to obtain beneficial effects and the relative merit of dietary intake of omega-3 polyunsaturated fatty acids versus supplements. This review looks at the evidence for the effects of omega-3 polyunsaturated fatty acids on various cardiac disorders and the risk factors for cardiac disease.
Dietary intake of fish is the best way to increase marine n-3 PFA intake. 1 gram per day of omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic supplement is equivalent to 55-85 g of fresh tuna, sardine, salmon or trot or 650 g Atalntic cod.
The amount of PUFA intake to educe triglycerides cannot be achieved by diet alone.
Marine n-3 PUFAs act as pleiotropic agents on the cardiovascular system with a diverse range of effects, most of which are beneficial. So far, the most important effect seems to be related to reduction in mortality after a myocardial infarction. Although findings from several studies have suggested the possibility of an anti¬arrhythmic effect, other clinical studies have not convincingly supported this mode of action. The overall effect of n-3 PUFAs in patients with coronary ischaemia without previous myocardial infarction is not established, with a potential benefit in the reduction of ischaemic coronary events set against an ongoing controversy over a possible rise in the risk of arrhythmic events. The anti-¬inflammatory, anti-atherosclerotic, and anti-immuno¬modulatory effects have not yet been proven to give clinical benefits.

Saravanan et al 2010 , Cardiovascular effects of marine omega- 3 fatty acids . The Lancet vol 376 pp 540-550

Survival factors

noreply@blogger.com (Martin Eastwood) — Mon, 16 Aug 2010 06:56:21 PDT

The factors in behaviour that can influence survival after quitting smoking have been
studied. Strong relationships has the strongest effect in improving survival. Having strong social relationships seems to have an effect on survival comparable to that of quitting smoking and larger than con¬trolling traditional risk factors, such as obes¬ity or hypertension. A meta-analysis of social relationships and mortality looked at 308849 participants aged 63.9, on average, at baseline; 29% died during the follow-up of 7.5 years.
Overall, strong social relationships improved the odds of survival by 5 %. Similar results were found for two aspects of relationships, defined by the researchers as structural (integration in social networks) and func¬tional (received or perceived social support), although the link with integration was some¬what stronger.
Reported in BMJ 14August 2010 vol 341 p 325

Japan and age

noreply@blogger.com (Martin Eastwood) — Mon, 16 Aug 2010 06:54:15 PDT

Longest lifespan Japan is struggling to cope with the rising welfare costs of its rapidly ageing society, as Japanese women continue to hold the 25-year record for the longest lifespan: an average of 86•44 years. This record is attributed to improvements in the treatment of cardiac disorders, strokes, and cancer, three of the main causes of death in Japan.
Lancet August 7th 2010

Clean water and the UN

noreply@blogger.com (Martin Eastwood) — Sun, 08 Aug 2010 00:41:58 PDT

Irrespective of politicking at the UN, 884 million people worldwide do not have regular access to clean water, and 2•6 billion do not have access to basic sanitation. The 2010 Millennium Development Goal 7 report states that the target of halving the number of people without access to safe water is on course to be met by 2015, but provision of sanitation is not. The practice of open defecation by 1•1 billion people is not only "an affront to human dignity", but also the key source of faecal-oral transmitted diseases such as diarrhoea, which causes 1•3 million deaths per year in children younger than 5 years.
A little more than 5 years through the UN General Assembly's Water for Life Decade, adequate supply of water and sanitation is far from universal. When the Human Rights Commission's report is published, the hope is that no country obstructs a binding commitment to provide clean water and sanitation for all. •
The Lancet August 7th 2010 p 390

Children's diet in UK by ethnicity

noreply@blogger.com (Martin Eastwood) — Thu, 05 Aug 2010 05:20:07 PDT

In the UK, South Asian adults have increased risks of CHD, type 2 diabetes and central obesity. Black African-Caribbeans, in contrast, have increased risks of type 2 diabetes and general obesity but lower CHD risk. There is growing evidence that the risk differences emerge in early life and that nutritional factors may be important. This study looks at the variations in nutritional composition of the diets of South Asian, black African-Caribbean and white European children, using 24h recalls of dietary intake collected during a cross-sectional survey of cardiovascular health in eighty-five primary schools in London, Birmingham and Leicester.
In all, 2209 children aged 9-10 years took part, including 558 of South Asian, 560 of black African-Caribbean and 543 of white European ethnicity. Compared with white Europeans, South Asian children reported higher mean total energy intake; their intake of total fat, polyunsaturated fat and protein (both absolute and as proportions of total energy intake) were higher and their intakes of carbohydrate as a proportion of energy (particularly sugars), vitamin C and D, Ca and haem Fe were lower.
These differences were especially marked for Bangladeshi children. Black African-Caribbean children had lower intakes of total and saturated fat (both absolute and as proportions of energy intake), Dietary Fibre , vitamin D and Ca. The lower total and saturated at intakes were particularly marked among black African children. Appreciable ethnic differences exist in the nutritional composition of children's diets, which may contribute to future differences in chronic disease risk.
Donin et al 2010 Nutritional composition of the diets of South Asian, black African-Caribbean and white European children in the United Kingdom: The Child Heart and Health Study in England (CHASE) British J Nutrition vol 104 276-285

pancreatic circadian rhythmn

noreply@blogger.com (Martin Eastwood) — Thu, 05 Aug 2010 04:53:57 PDT

Circadian clocks have profound effects on metabolism and behaviour , in plants and mammals.
In 1972, a study demonstrated that within the brain hypothalamus, the suprachiasmatic nucleus, which is close to the optic nerves, is required for daily rhythms in animal behaviour.. The suprachias¬matic nucleus receives light signals through the optic nerves, and so uses daylight cues to set the clock time and to couple light-dark transi¬tions to behavioural outputs.
Subsequent genetic studies identified several genes that mediate rhythmic behaviour.
The mammalian circadian clock is a molecular oscillator based on a nega¬tive- feedback loop in which the transcription factors CLOCK (or the related protein NPAS2) and BMALl work together to drive the expres¬sion of many genes, including the period (PERl, PER2 and PER3) and the cryptochrome (CRYl and CRY2) proteins.

Now it is clear that clocks outside the suprachiasrnatic nucleus have physiological roles?
First, expression of enzymes, transporters and receptors that regulate metabolism fluctuate robustly throughout the day.
Second circadian clocks outside the suprachiasmatic nucleus are adjusted on the basis of feeding time rather than the light-dark schedule For example, the cellular energy sensor AMPK controls the stability of cryptochromes and may contribute to nutrient entrainment of the clock in the liver.
Marcheva et al. have shown that the mouse pan¬creas also has a functional circadian clock, with individual pancreatic islets having clock function even when outside their normal tissue environment. The islet clock seems to consist of the same components as other mammalian circadian clocks, and drives rhythmic expression of genes involved in insulin sensing, glucose sensing, and islet growth and development. These clocks are therefore crucial for the specific metabolic needs and functions of islet cells .
Lamia and Evans 2010 Tick, tock , a β-cell clock Nature vol 466, 571-2
Marcheva et al 2010 Disruption of the clock components CLOCK and BMAL1 leads to hyper- insulinaemia and diabetes Nature vol 466 627-631

HDL cholesterol and cardiovascular risk

noreply@blogger.com (Martin Eastwood) — Thu, 05 Aug 2010 04:20:05 PDT

Cardiovascular disease is the leading cause of death worldwide. Reducing concentrations of LDL cholesterol with statin therapy has resulted in reductions of 23% in cardiovascular risk for every 1•03 mmol/L (40 mg/dL) decrease in LDL cholesterol. However, despite a reduction in LDL cholesterol with high-dose statins to 1•6 mmol/L in patients with stable coronary heart disease, and to 2•0 mmol/L in those with acute coronary syndrome, the risk of cardiovascular disease remains substantial at 8-7% after 4•9 years of follow-up, and 22-4% after 24 months' follow-up, respectively. Low concentrations of HDL cholesterol might contribute to this residual cardiovascular risk."
Population-based studies show that low concentrations of HDL cholesterol «1•03 mmol/L) are a risk factor for cardiovascular disease. thus increasing HDL cholesterol by 0•03 mmol/L can reduce cardiovascular risk by 2-3% per year.
Paul Ridker and colleagues, for the JUPITER Trial Study Group, challenge whether HDL cholesterol concentrations are predictive of cardiovascular risk at low concentrations of LDL cholesterol.
Raising HDL cholesterol remains a major treatment strategy for the reduction of cardiovascular risk in the large majority of patients who do not have very low LDL cholesterol; the problem, in most cases, is how to achieve this strategy.
Lifestyle changes, such as more aerobic exercise, weight loss, smoking cessation, moderate alcohol intake, and dietary changes might result in modest increases in HDL choiesterol.
Drugs that specifically raise HDL cholesterol concentrations are less available, with niacin being the most effective current agent. Others include the fibrates, the thiazolidinediones, and the qlitazars.
Hausenloy et al 2010 Dissociating HDL cholesterol from cardiovascular risk Lancet vol 376, pp 305-6
Ridker PM et al 2010 HDL cholesterol and residual risk of first cardiovascular events after events after treatment with statin : an analysis from the JUPITER trial vol 376 333-39

Flavonoids and immunity

noreply@blogger.com (Martin Eastwood) — Fri, 30 Jul 2010 10:02:06 PDT

Epidemiological evidence suggests that a high intake of plant foods is associated with lower risk of chronic diseases.
The mechanism of action and the components involved in this effect have not been clearly identified .
A class of secondary metabolites present in a wide range of plant foods: the flavonoids, have different biological roles.
The anti-inflammatory actions of flavonoids in vitro or in cellular models involve the inhibition of the synthesis and activities of different pro-inflammatory mediators such as eicosanoids, cytokines, adhesion molecules and C-reactive protein.
Molecular activities of flavonoids include inhibition of transcription factors such as NF-KB and activating protein-I (AP-l), as well as activation of nuclear factor-erythroid 2-related factor 2 (Nrf2).
In vitro evidence of activity is limited as non-physiological concentrations are used and in vivo flavonoids are extensively metabolized to molecules with different chemical structures and activities compared with the ones originally present in the food.
Human studies investigating the effect of flavonoids on markers of inflammation are insufficient, and are mainly focused on flavonoid-rich foods but not on pure molecules. Most of the studies lack assessment of flavonoid absorption or fail to associate an effect on inflammation with a change in circulating levels of flavonoids.
Human trials with appropriate placebo and pure flavonoid molecules are needed to clarify if flavonoids represent ancillary ingredients or key molecules involved in the anti-inflammatory properties of plant foods.
Serafini 2010 Antioxidants and the immune system Flavonoids as anti-inflammatory agents Proceedings of Nutrition Society vol 69 273-78

whole-grain cereals

noreply@blogger.com (Martin Eastwood) — Fri, 23 Jul 2010 23:07:57 PDT

This review is a comprehensive overview of the benefits of whole grain cereals.
Epidemiological studies have shown that whole-grain cereals can protect against obesity, diabetes, cardio vascular disease and cancers.
The specific effects of food structure (increased satiety, reduced transit time and glycaemic response), fibre (improved faecal bulking and satiety, viscosity and SCFA production, and/or reduced glycaemic response) and Mg (better glycaemic homeostasis through increased insulin secretion), together with the antioxidant and anti-carcinogenic properties of numerous bioactive compounds, especially those in the bran and germ (minerals, trace elements, vitamins, carotenoids, polyphenols and alkylresorcinols), are well-recognised mechanisms in this protection.
Recent findings, the exhaustive listing of bioactive compounds found in whole-grain wheat, their content in whole-grain, bran and germ fractions and their estimated bioavailability, have led to new hypotheses.
The involvement of polyphenols in cell signalling and gene regulation, and of sulfur compounds, lignin and phytic acid should be considered in antioxidant protection.
Whole-grain wheat is also a rich source of methyl donors and lipotropes (methionine, betaine, choline, inositol and folates) that may be involved in cardiovascular and/or hepatic protection, lipid metabolism and DNA methylation. Potential protective effects of bound phenolic acids within the colon, of the B-complex vitamins on the nervous system and mental health, of oligosaccharides as prebiotics, of compounds associated with skeleton health, and of other compounds such as a-linolenic acid, policosanol, melatonin, phytosterols and para-aminobenzoic acid are important.
Any seed is a start up pack for the new plant and must contain all that is required for a new life. All seeds must be nutritionally of value.
Finally, benefits of nutrigenomics to study complex physiological effects of the 'whole-grain package', and the most promising ways for improving the nutritional quality of cereal products are _discussed.
Fardet (2010 ) New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? Nutrition research Reviews vol 23 65-134

vitamin D receptor genetic variants

noreply@blogger.com (Martin Eastwood) — Fri, 23 Jul 2010 23:03:25 PDT

Vitamin D insufficiency has been implicated in many musculoskeletal and extra skeletal diseases, which has led to substantial interest in the determinants of vitamin D status.
This paper by Wang et al Our findings establish a role for common genetic variants in regulation of circulating 25-hydroxyvitamin D concentrations. The presence of harmful alleles at the three confirmed loci more than doubled the risk of vitamin D insufficiency. These findings improve - our understanding of vitamin D homoeostasis and could assist identification of a subgroup of the white population who are at risk of vitamin D insufficiency.
DHCR7/NADSYNl is a novel locus for association with vitamin D status, DHCR7 encodes the enzyme 7-dehydrocholesterol (7-DHC) reductase, which converts 7-DHC to cholesterol, thereby removing the substrate from the synthetic pathway of vitamin D, a precursor of 25-hydroxyvitamin DJ. Rare mutations in DHCR7lead to Smith-Lernli-Opitz syndrome, which is characterised by reduced activity of 7-DHC reductase, accumulation of 7-DHC, low cholesterol, and many congenital abnormalities." Mutations in DHCR7 might also confer a competitive advantage to heterozygous carriers, because high concentrations of 7-DHC could provide protection against rickets and osteomalacia from hypovitaminosis D.The finding that common variants at DHCR7 are strongly associated with circulating 25-hydroxyvitamin D concentrations suggests that this enzyme could have a larger role in regulation of vitamin D status than has previously been recognised.
The gene at the second locus, CYP2Rl, encodes a hepatic microsomal enzyme. CYP2Rl could be the enzyme underlying 25-hydroxylation of vitamin D in the liver, but this suggestion is uncertain because many other enzymes with 25-hydroxylase activity in vitro have been described These finding that common variants at the CYP2Rl locus are associated with circulating 25-hydroxyvitamin D concentrations is the strongest evidence so far that CYP2R1 is the enzyme underlying the crucial first step in vitamin D metabolism.
The third gene, GC, encodes vitamin D binding protein, which is a 52-59 kDA protein synthesised in the liver that binds and transports vitamin D and its metabolites (including25-hydroxyvitarninDand1,25-dihydroxyvitamin D).
Wang et al 2010 Common genetic determinants of vitamin D insufficiency : a genome – wide association study. Lancet vol 376 pp 180-88

sun and vitamin D

noreply@blogger.com (Martin Eastwood) — Fri, 23 Jul 2010 23:00:53 PDT

The public health message is : avoid the sun to prevent melanoma and other forms of skin cancer. But exposure to sunlight is important for vitamin D synthesis, and vitamin D deficiency causes rickets and osteomalacia, contributes to osteoporosis.
Ultraviolet B radiation produces 90% of vitamin D in human beings, only a very small proportion can be obtained through diet. However, at high latitudes, levels of sunlight in winter are often so low that vitamin D insufficiency is common. Avoidance of the sun's rays by covering up or use of sunscreen can compound this problem, and is thought to have contributed to a recent increase in metabolic bone disease. Cancer Research UK recognises the need to balance skin cancer prevention with generation of adequate vitamin D, but specified that "the skin efficiently produces vitamin D at levels of sun exposure below those that cause sunburn .. when it comes to sun exposure, little and often is best". Australia's SunSmart guidelines underwent a revision to reflect this balance in 2006-07.
A major concern is that people might seek prolonged sun exposure without protection to boost vitamin D synthesis. Indeed, the American Academy of Dermatology argues that the risks of sun exposure outweigh the benefits, advocating instead for dietary supplementation as a safe source of vitamin D. A report published in the British Journal of Nutrition emphasises that in the UK, a unified approach to vitamin D supplementation is needed to address deficiency in pregnant women and avoid life¬ threatening complications for their babies.
Leader Lightening the way to better health : vitamin D Lancet vol 376 p 142
Brit J Nutr 2010 ; DO1; 1017/SOOO7114510002436

equation to predict tissue gain

noreply@blogger.com (Martin Eastwood) — Fri, 23 Jul 2010 22:57:39 PDT

Predicting the magnitude and rate of weight gain for a given increase of energy intake requires a model of whole-body energy expenditure that includes the energy cost of tissue deposition.
Hall in this paper introduces a mathematical framework for modelling energy expenditure that elucidates conceptual problems with the classical Kielanowski method for estimating the efficiencies of body fat and protein deposition.
An alternative approach uses the theoretical biochemical efficiencies for protein and fat synthesis in combination with models of energy expenditure that include body fat and protein turnover costs. He illustrates this alternative approach using a simple mathematical model applied to previously published data from growing rats and human infants and compare the simple model results with the classical Kielanowski model.
While both models fit the data reasonably well (R 2 > 0•87 in rats and R 2 > 0•67 in infants), the Kielanowski method resulted in parameter estimates that varied widely across experiments, had poor precision, and occasionally produced efficiency estimates greater than 1. In contrast, the new method provided precise parameter values and revealed consistencies across different experiments. The proposed mathematical framework has implications for interpreting studies of animal nutrition as well as providing a roadmap for future modelling efforts.
Hall 2010 Mathematical modelling of energy expenditure during tissue deposition Brit J Nutrition vol 104 4-7

faecal viral population

noreply@blogger.com (Martin Eastwood) — Wed, 21 Jul 2010 01:46:45 PDT

The variety of Viruses and their life cycles are poorly understood in the human gut and other body habitats.
Phages and their encoded functions may provide information of a human microbiota and of microbial community responses to various disturbances.
This paper reports sequencing of the viromes (metagenomes) of virus-like particles isolated from faecal samples collected from healthy adult female monozygotic twins and their mothers at three time points over a one-year period.
They compared these results sets with data sets of sequenced bacterial16S ribosomal RNA genes and total-faecal-community DNA.
The co-twins and their mothers share a significantly greater degree of similarity in their faecal bacterial communities than do unrelated individuals.
In contrast, viromes are unique to individuals regardless of their degree of genetic relatedness. Despite remarkable interpersonal variations in viromes and their encoded functions, intra personal diversity is very low, with >95% of virotypes retained over the period surveyed, and with viromes dominated by a few temperate phages that exhibit remarkable genetic stability.
Reyes et al 2010 Viruses in the faecal microbiota of monozygotic twins and their mothers Nature vol 466 pp 334-338

Obesity and sexual health

noreply@blogger.com (Martin Eastwood) — Wed, 21 Jul 2010 01:44:04 PDT

Obesity and sex are subjects that doctors find especially difficult to discuss with patients, despite evidence that such discussions help. Although short conversations (three to five minutes) during routine Visits can contribute to changes in behaviour, such as increasing physical activ¬ity, eating less fat, and losing weight, most primary care professionals do not talk to their patients about weight.
Bajos and colleagues' study of 12 364 French men and women aged 18-69 found that obese men and women are at greater risk of negative sexual outcomes than their non¬obese counterparts. This was particularly true for obese women, who were 30% less likely to report a sexual part¬ner in the past 12 months, whereas obese men were 700/0 less likely to report more than one partner in the same period and 2.6 times as likely to report erectile dysfunc¬tion. Although no other differences were found in indices of sexual function in existing relationships, obese women were five times as likely to have met their partner on the internet, more likely to have an obese partner, and less likely to view sex as important for personal life balance.
The factors that underlie these observations of self reported sexual experience and the directions of causal¬ity cannot be determined from a cross sectional study,
Obese women in the 18- 29 year old age group were less likely to report that they used oral contraception or sought contraceptive advice in the past year, and, most startling of all, they were 4.3 times more likely to report unintended preg¬nancy. Obesity in pregnancy is a major public health concern. Obesity in pregnancy is associated with markedly increased mater¬nal and neonatal morbidity and mortality, and increased healthcare costs. It is the principal maternal health project of the Centre for Maternal and Child Enquiries (CMACE) for 2008- 2011, and it is the subject of a new joint guide¬line from CMACE and the Royal College of Obstetricians and Gynaecologists.' So if the message of this paper-that obese women have nearly five times the risk of unwanted pregnancy-is reproducible in other populations, this shoul.d be a matter of concern for public health and prac¬titioners in reproductive health.
The data on contraception need cautious interpreta¬tion, however, because they focus purely on oral contra¬ception and condoms, ignoring long acting reversible contraceptives, which the UK's National Institute for Health and Clinical Excellence (NICE) recommends as particularly suitable for obese women.
Goldbeck-Wood (2010) Obesity and poor sexual health outcomes BMJ vol 341 pp 56-7
Bajos (2010) Sexuality and obesity, a gender perspective: result from French national randomn probability survey of sexual behaviours . BMJ vol 340, p 84

Histone methylation and longevity

noreply@blogger.com (Martin Eastwood) — Tue, 20 Jul 2010 12:51:25 PDT

The process of ageing and longevity may be controlled biologically by specific alterations in chromatin state. The link between chromatin and ageing has mostly focused on histone deacetylation by the Sir2 family, but less is known about the role of other histone modifications in longevity.
Histone methylation has a crucial role in development and in maintaining stem cell pluri¬potency in mammals.
In this paper Greer et al identify the ASH-2 trithorax complex, which trirnethylates histone H3 at lysine 4 (H3K4), as a regulator of lifespan in Caenorhabditis elegans in a directed RNA interference (RNAi) screen in fertile worms.
Deficiencies in members of the ASH-2 complex-ASH-2 itself, WDR-5 and the H3K4 methyltransferase SET-2--extend worm lifespan.
Conversely, the H3K4 demethylase RBR-2 is required for normallifespan, consistent with the idea that an excess ofH3K 4 trimethylation-a mark associated with active chromatin¬is detrimental for longevity.
Lifespan extension induced by ASH-2 complex deficiency requires the presence of an intact adult germ¬line and the continuous production of mature eggs. ASH-2 and RBR-2 act in the germline, at least in part, to regulate lifespan and to control a set of genes involved in lifespan determination.
These results indicate that the longevity is regulated by an H3K4 methyltransferase/demethylase complex acting in the C. elegans germline.

Greer et al ( 2010 ) Members of the H3K4 trimethylation complex regulate llfespan in a germ line-dependent manner in C. elegans Nature vol 466 pp 383-387

China and water

noreply@blogger.com (Martin Eastwood) — Tue, 20 Jul 2010 12:46:53 PDT

A crisis is developing beneath China's farms and cities. With about 20% of the world's popula-tion but only about 5-7% of global freshwater resources, China draws heavily on ground¬water. Those reserves are being depleted at an alarming rate in some regions and are badly polluted in many others.
The water crisis is not unique to China, but the problem here is orders of magnitude bigger than anywhere else:'
Groundwater is used to irrigate more than 40% of China's farmland, and for about 70% of the drinking water in the dry northern and north¬western regions.
During the past few decades groundwater extraction has increased by about 2.5 billion cubic metres per year. Groundwater levels of the arid North China Plain have dropped as fast as 1 metre a year between 1974 and 2000, forcing people to dig hundreds of metres to access fresh water.
Water is scarce for two-thirds of China's 660 cities. As China's economy expands, so will its demand for water. The country will consume 750 billion cubic metres of water a year by 2030, about 90% of the total amount of usable water resources in the country..
Pollution is also putting the system under pressure. In southern and southeastern China, which have seen rapid economic development, groundwater is now laden with heavy metals and other pollutants. 90% of groundwater is polluted, 60% of it seriously so.

The government hopes that a massive system of canals and pipes, to funnel 45 billion cubic metres of water a year from China's moist south to its arid north, will alleviate groundwater depletion once it is completed in 2050.

Climate contributed only about 10-30% of the water-table depletion in three regions of China. The majority of the depletion was down to farming practice: "There is much room for improvement in terms of more effective water management.
Arguably, the biggest improvement could come in the agriculture sector, which already uses 70% of the Country'S fresh water. To boost grain production, for example, China has a double-cropping system of growing wheat in winter and maize in summer. But because there is very little precipitation on the North China Plain in winter, this draws deeply on groundwater supplies. The country could import grain, and synchronize crop production with the climate by ending the cultivation of winter wheat and growing maize for more of the year.
Qiu 2010 China faces up to groundwater crisis nature vol 466 p 308

histones and cancer

noreply@blogger.com (Martin Eastwood) — Thu, 15 Jul 2010 02:33:08 PDT

Post-translational modification of histones provides an important regulatory platform for processes such as gene transcription and DNA damage repair. It has become increasingly apparent that the misregulation of histone modification, which is caused by the deregulation of factors that mediate the modification installation, removal and/or interpretation, actively contributes to human cancer. In this Review, the authors summarize recent advances in understanding the interpretation of certain histone methylations by plant homeodomain finger-containing proteins, and how misreading, miswriting and mis-erasing of histone methylation marks can be associated with oncogenesis and progression. These observations provide a greater mechanistic understanding of epigenetic alterations in human cancers and might also help direct new therapeutic interventions in the future.
Chi et al (2010 ) Covalent histone modifications — miswritten, misinterpreted and mis-erased in human cancers. Nature Reviews Cancer 10, 457-469