Imperial College London

Michael A Crawford PhD, FSB, FRCPath

Faculty of MedicineDepartment of Surgery & Cancer

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3315 7899michael.crawford Website CV

 
 
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Location

 

H 3.34Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Publication Type
Year
to

227 results found

Ogundipe E, Tusor N, Wang Y, Johnson MR, Edwards AD, Crawford MAet al., 2018, Randomized controlled trial of brain specific fatty acid supplementation in pregnant women increases brain volumes on MRI scans of their newborn infants, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 138, Pages: 6-13, ISSN: 0952-3278

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Crawford MA, Thabet M, Wang Y, Broadhurst CL, Schmidt WFet al., 2018, A theory on the role of pi-electrons of docosahexaenoic acid in brain function. The six methylene-interrupted double bonds and the precision of neural signaling, OCL-OILSEEDS AND FATS CROPS AND LIPIDS, Vol: 25, ISSN: 1258-8210

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Crawford MA, Thabet M, Wang Y, 2018, An introduction to a theory on the role of pi-electrons of docosahexaenoic acid in brain function - The Quantum Brain, OCL - Oilseeds and fats, crops and lipids, Vol: 25, ISSN: 1258-8210

In Part I, we discuss the background to views on brain function and our thesis that it is conducted by π-electrons which perform sensory reception, memory, action, cognition and consciousness. Our thesis is consistent with the classical views of ion movement and synaptic protein strengthening. However, protein based views contain no element of precision for the signal. Precision is essential for true signal transduction of sensory input and the faithful execution of learnt neural pathways. In Part II, we incorporate these principles to discuss the mechanism whereby electron function adds precision of signal energy to the process through the Pauli Exclusion Principle. The Huxley-Hodgkin (HH) account of neural function describes the movement of sodium, potassium and calcium ions to create electrochemical potentials across membranes with well-established mathematical and experimental support. To explain learning, consciousness and perception, others have claimed brain function depends on protein synthesis or RNA coding. Some consider super position and collapse as the computational mechanism. This however is fragile with no mechanism described to protect from natural collapse and decoherence at the temperatures of the brain. A novel approach was adopted by Penrose and Hammeroff who describe consciousness as a function of ʻobjective reduction’ (ʻOR’) of the quantum state. This orchestrated OR activity (ʻOrch OR’) is taken to result in moments of conscious awareness and/or choice (Hameroff S, Penrose R. 2014 Consciousness in the universe: a review of the ʻOrch OR’ theory. Phys Life Rev 11(1): 39–78. Doi: 10.1016/j.plrev.2013.08.002. Epub 2013 Aug 20). Orch-OR operates in principle in protein tubules of neurons. This concept is non-computational and has received much attention with a convincing advocacy and its share of criticism. The advocacy includes the fossil record of organisms that emerged throughout the first Cambrian period with on

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Stark AH, Reifen R, Crawford MA, 2016, Past and Present Insights on Alpha-linolenic Acid and the Omega-3 Fatty Acid Family., Crit Rev Food Sci Nutr, Vol: 56, Pages: 2261-2267

Alpha-linolenic acid (ALA) is the parent essential fatty acid of the omega-3 family. This family includes docosahexaenoic acid (DHA), which has been conserved in neural signaling systems in the cephalopods, fish, amphibian, reptiles, birds, mammals, primates, and humans. This extreme conservation, in spite of wide genomic changes of over 500 million years, testifies to the uniqueness of this molecule in the brain and affirms the importance of omega-3 fatty acids. While DHA and its close precursor, eicosapentaenoic acids (EPA), have received much attention by the research community, ALA, as the precursor of both, has been considered of little interest. There are many papers on ALA requirements in experimental animals. Unlike humans, rats and mice can readily convert ALA to EPA and DHA, so it is unclear whether the effect is solely due to the conversion products or to ALA itself. The intrinsic role of ALA has yet to be defined. This paper will discuss both recent and historical findings related to this distinctive group of fatty acids, and will highlight the physiological significance of the omega-3 family.

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Ogundipe E, Johnson MR, Wang Y, Crawford MAet al., 2016, Peri-conception maternal lipid profiles predict pregnancy outcomes, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 114, Pages: 35-43, ISSN: 0952-3278

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Crawford MA, Wang Y, Forsyth S, Brenna JTet al., 2015, The European Food Safety Authority recommendation for polyunsaturated fatty acid composition of infant formula overrules breast milk, puts infants at risk, and should be revised, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 102, Pages: 1-3, ISSN: 0952-3278

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Bueno AA, Brand A, Neville MM, Lehane C, Brierley N, Crawford MAet al., 2015, Erythrocyte phospholipid molecular species and fatty acids of Down syndrome children compared with non-affected siblings, BRITISH JOURNAL OF NUTRITION, Vol: 113, Pages: 72-81, ISSN: 0007-1145

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Cunnane SC, Crawford MA, 2014, Energetic and nutritional constraints on infant brain development: Implications for brain expansion during human evolution, JOURNAL OF HUMAN EVOLUTION, Vol: 77, Pages: 88-98, ISSN: 0047-2484

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Crawford MA, Broadhurst CL, Guest M, Nagar A, Wang Y, Ghebremeskel K, Schmidt WFet al., 2014, A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution (vol 88, pg 5, 2013), PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 91, Pages: 233-233, ISSN: 0952-3278

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Crawford MA, Broadhurst CL, Cunnane S, Marsh DE, Schmidt WF, Brand A, Ghebremeskel Ket al., 2014, Nutritional Armor in Evolution: Docosahexaenoic Acid as a Determinant of Neural, Evolution and Hominid Brain Development, Military Medicine, Vol: 179, Pages: 61-75, ISSN: 1930-613X

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Brenna JT, Burdge GC, Crawford MA, Clayton P, Cunnane SC, Gow R, Hibbeln JR, Sinclair AJ, Stein J, Willatts Pet al., 2014, RE: Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 106, ISSN: 0027-8874

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Gow RV, Vallee-Tourangeau F, Crawford MA, Taylor E, Ghebremeskel K, Bueno AA, Hibbeln JR, Sumich A, Rubia Ket al., 2013, Omega-3 fatty acids are inversely related to callous and unemotional traits in adolescent boys with attention deficit hyperactivity disorder, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 88, Pages: 411-418, ISSN: 0952-3278

JOURNAL ARTICLE

Gow RV, Sumich A, Vallee-Tourangeau F, Crawford MA, Ghebremeskel K, Bueno AA, Hibbeln JR, Taylor E, Wilson DA, Rubia Ket al., 2013, Omega-3 fatty acids are related to abnormal emotion processing in adolescent boys with attention deficit hyperactivity disorder, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 88, Pages: 419-429, ISSN: 0952-3278

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Daak AA, Ghebremeskel K, Hassan Z, Attallah B, Azan HH, Elbashir MI, Crawford Met al., 2013, Reply to UN Das., Am J Clin Nutr, Vol: 97, Pages: 1416-1417

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Sumich AL, Matsudaira T, Heasman B, Gow RV, Ibrahimovic A, Ghebremeskel K, Crawford MA, Taylor Eet al., 2013, Fatty acid correlates of temperament in adolescent boys with attention deficit hyperactivity disorder., Prostaglandins Leukot Essent Fatty Acids, Vol: 88, Pages: 431-436

Atypical fatty acid metabolism has been reported in attention deficit hyperactivity disorder (ADHD), however, its relationship with temperament in this population is unclear. The current study investigated the association between blood levels of fatty acids implicated in brain structure and function (omega-3, omega-6, omega-9) and personality traits of stability (neuroticism, conscientiousness and agreeableness) and plasticity (extraversion and openness). Twenty right-handed adolescent boys with ADHD completed a self-report NEO-FFI personality questionnaire, and had fatty acid content assessed from red blood using gas chromatography. Pearson's correlations showed no significant associations between omega-3 levels and personality. After correction for multiple comparisons, Adrenic Acid (C22:4n6) was inversely associated with stability. Oleic acid (C18:1n9) was positively associated with plasticity. Results are in line with a role of fatty acids in brain function. They suggest that those fatty acids that are involved in myelination (Adrenic, Oleic) have the strongest associations with temperament in adolescents with ADHD.

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Crawford MA, Wang Y, Forsyth S, Brenna JTet al., 2013, New European Food Safety Authority recommendation for infant formulae contradicts the physiology of human milk and infant development., Nutr Health, Vol: 22, Pages: 81-87, ISSN: 0260-1060

The European Food Safety Authority (EFSA) has concluded from a limited review of the literature that although docosahexaenoic acid (DHA) was required for infant formula, arachidonic acid was not 'even in the presence of DHA'. The EFSA report mistakes a nutrient ubiquitous in the diets of infants, and with wide-ranging effects, for an optional drug targeted to a particular outcome that is properly excluded when no benefit is found for that particular outcome. The EFSA's conclusion is not evidence-based. Its conclusions are grounded in trials which tested functionality of DHA, not arachidonic acid. Arachidonic acid has very different biological functions, for instance, in the vasculature and in specific aspects of immunity. None of the trials cited tested any property specific to arachidonic acid. The test of time through natural selection and human evolution has resulted in milk composition in which arachidonic acid and its long-chain polyenoic family members are conserved and occupy a prominent position. As DHA suppresses arachidonic acid, an infant formula with DHA and no arachidonic acid runs the risk of cardio- and cerebrovascular morbidity through suppression of the favourable eicosanoid derivatives of arachidonic acid and cell structural integrity. The EFSA recommendation should be rejected forthwith as unsafe and risking lifelong disability.

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Crawford MA, Broadhurst CL, Guest M, Nagar A, Wang Y, Ghebremeskel K, Schmidt WFet al., 2013, A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution, PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, Vol: 88, Pages: 5-13, ISSN: 0952-3278

JOURNAL ARTICLE

Crawford MA, 2013, Diet and cancer and heart disease., Nutr Health, Vol: 22, Pages: 67-78, ISSN: 0260-1060

The modern Western diet bears little resemblance to the diet which forged the human genome over many million years. The change in basic food structure is operating to distort biology even before conception and into late years, with the epidemic of obesity and diabetes likely to lead to stroke, heart disease, and now dementia, being flagged as a consequence. In addition, mental ill health is overtaking all other burdens of ill health, and almost certainly has its roots in early disturbance of brain development. Whilst lifestyle will be playing its part, there can be little doubt that the common denominator is the aberrations in food development, predominantly in the last century. It seems it is time to reassess food policy. The principle of food production should be nutrition and human health. The globalisation of a food structure linked to such disorders and their appearance globally in response asks that steps be taken to protect other countries from making the same mistakes.

JOURNAL ARTICLE

Daak AA, Ghebremeskel K, Hassan Z, Attallah B, Azan HH, Elbashir MI, Crawford Met al., 2013, Effect of omega-3 (n-3) fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-controlled trial., Am J Clin Nutr, Vol: 97, Pages: 37-44

BACKGROUND: Blood cell aggregation and adherence to vascular endothelium and inflammation play a central role in vaso-occlusive crisis in sickle cell disease. The antiaggregatory, antiadhesive, antiinflammatory, and vasodilatory omega-3 (n-3) fatty acids (DHA and EPA) are significantly reduced in patients with the disease. OBJECTIVE: The aim was to investigate the therapeutic potential of omega-3 fatty acids for patients with homozygous sickle cell disease in a randomized, placebo-controlled, double-blind trial. DESIGN: One hundred forty patients recruited from a single center in Sudan were randomly assigned and received, daily, 1 (age 2-4 y), 2 (age 5-10 y), 3 (age 11-16 y), or 4 (age ≥17 y) omega-3 capsules containing 277.8 mg DHA and 39.0 mg EPA or placebo for 1 y. Of these patients, 128 were followed up and the data were obtained. The primary and secondary endpoints-rates of clinical vaso-occlusive crisis and hemolytic events, blood transfusion rate, school attendance, and blood count-were analyzed by intention-to-treat analysis (n = 140). RESULTS: Omega-3 treatment reduced the median rate of clinical vaso-occlusive events (0 compared with 1.0 per year, P < 0.0001), severe anemia (3.2% compared with 16.4%; P < 0.05), blood transfusion (4.5% compared with 16.4%; P < 0.05), white blood cell count (14.4 ± 3.3 compared with 15.6 ± 4.0 ×10(3)/μL; P < 0.05), and the OR of the inability to attend school at least once during the study period because of illness related to the disease to 0.4 (95% CI: 0.2, 0.9; P < 0.05). CONCLUSION: The findings of this trial, which need to be verified in a large multicenter study, suggest that omega-3 fatty acids can be an effective, safe, and affordable therapy for sickle cell anemia. This trial was registered with Current Controlled Trials as ISRCTN80844630.

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Crawford MA, 2012, The crisis in nutrition and poverty., Nutr Health, Vol: 21, Pages: 205-208, ISSN: 0260-1060

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Msika O, Brand A, Crawford MA, Yavin Eet al., 2012, NGF blocks polyunsaturated fatty acids biosynthesis in n-3 fatty acid-supplemented PC12 cells., Biochim Biophys Acta, Vol: 1821, Pages: 1022-1030, ISSN: 0006-3002

Regulation of polyunsaturated fatty acid (PUFA) biosynthesis in proliferating and NGF-differentiated PC12 pheochromocytoma cells deficient in n-3 docosahexaenoic acid (DHA 22:6n-3) was studied. A dose- and time-dependent increase in eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid (DPA, 22:5n-3) and DHA in phosphatidylethanolamine (PtdEtn) and phosphatidylserine (PtdSer) glycerophospholipids (GPL) via the elongation/desaturation pathway following alpha-linolenic acid (ALA, 18:3n-3) supplements was observed. That was accompanied by a marked reduction of eicosatrienoic acid (Mead acid 20:3n-9), an index of PUFA deficiency. EPA supplements were equally effective converted to 22:5n-3 and 22:6n-3. On the other hand, supplements of linoleic acid (LNA, 18:2n-6) were not effectively converted into higher n-6 PUFA intermediates nor did they impair elongation/desaturation of ALA. Co-supplements of DHA along with ALA did not interfere with 20:5n-3 biosynthesis but reduced further elongation to 22-hydrocarbon PUFA intermediates. A marked decrease in the newly synthesized 22:5n-3 and 22:6n-3 following ALA or EPA supplements was observed after nerve growth factor (NGF)-induced differentiation. NGF also inhibited the last step in 22:5n-6 formation from LNA. These results emphasize the importance of overcoming n-3 PUFA deficiency and raise the possibility that growth factor regulation of the last step in PUFA biosynthesis may constitute an important feature of neuronal phenotype acquisition.

JOURNAL ARTICLE

Neville MM, Geppert J, Min Y, Grimble G, Crawford MA, Ghebremeskel Ket al., 2012, Dietary fat intake, body composition and blood lipids of university men and women., Nutr Health, Vol: 21, Pages: 173-185, ISSN: 0260-1060

BACKGROUND: Cardiovascular disease rates are high in the U.K., particular in men, and are related to dietary fat intake. We conducted a pilot study to investigate relationships between saturated and unsaturated dietary fat intakes, body composition and blood lipid parameters in Caucasian men and women at university. METHODS: Volunteers (52 men and 52 women; age range 20-50 years) were recruited from staff and students of London Metropolitan University. Dietary intake, body composition, blood pressure and fasting blood glucose and lipids were assessed. Gender differences between the measured variables and their relationships were assessed by Mann-Whitney U-test, and by multi-linear (stepwise) regression, respectively. RESULTS: Men consumed more saturated fat (29.5 vs. 20.5 g/day, p < 0.001), and had elevated levels of glucose (5.34 + 0.74 vs. 4.85 + 0.49 mmol/l, p < 0.001), low-density lipoprotein (LDL) cholesterol (2.99 + 1.5 vs. 2.62+ 0.74 mmol/l, p < 0.05), systolic blood pressure (126.4 + 11.0 vs. 112.6 + 17.2 mm/Hg, p < 0.001), and lower high-density lipoprotein (HDL) cholesterol (1.41 ± 0.34 vs. 1.83 ± 0.43, p < 0.001). Saturated fat was positively associated with total body fat ( p < 0.05), trunk fat ( p < 0.001), HDL cholesterol ( p < 0.05) and systolic blood pressure ( p < 0.001) in women, while in men docosahexaenoic acid and total cholesterol ( p < 0.05), total omega-3 fatty acids and LDL cholesterol ( p < 0.001), total omega-3 fatty acids and triglycerides ( p < 0.01) were positively related. Similar n-3 fatty acid intakes were reported in nutritionally aware students and other university subjects. CONCLUSIONS: The data of this study indicate gender-related differences in response to dietary fat, and widespread low compliance with n-3 fatty acid recommendations. Although the men are highly health conscious and physically active, their blood lipid levels are indicative of a risk of cardiovascular disease. I

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Nyuar KB, Khalil AKH, Crawford MA, 2012, Dietary intake of Sudanese women: a comparative assessment of nutrient intake of displaced and non-displaced women., Nutr Health, Vol: 21, Pages: 131-144, ISSN: 0260-1060

OBJECTIVES: To determine the daily intake of essential micro- and macronutrients in Sudanese women, with specific focus on dietary fat and essential fatty acids, and compare the dietary intakes of internally displaced women with those of the non-displaced population. METHODS: Dietary intakes of displaced southern (n=44) and non-displaced southern (n=30) and northern (n=39) Sudanese women were obtained by single 24-hour recall method, and daily nutrient intakes were calculated using 'Foodbase' nutritional software. The displaced women were recruited from Mayo and Soba Aradi camps, south of Khartoum city; and non-displaced southern and northern Sudanese women were recruited from antenatal clinics, universities, hospitals and the community in Khartoum city and Omdurman, Sudan. RESULTS: Carbohydrates provided over 60% of dietary energy for all the Sudanese women groups. The displaced women had significantly lower intake of energy (1744 ± 344 kcal/d), starch (p<0.001) and carbohydrates (312 ± 11 g/d, p<0.01) than both non-displaced southern (1972 ± 229 kcal/d energy, 358 ± 56 g/d carbohydrates) and northern Sudanese women (1988 ± 226 kcal/d energy, 357 ± 56g/d carbohydrates). Fat intake was also lower in the displaced group (34.1 ± 11.9 g/d) than in the non-displaced counterpart (38.5 ± 10.2 g/d) (p<0.05), but was not significantly different from northern Sudanese women (37.6 ± 10.6, p>0.05). Intakes of iodine (33.60-56.96 µg/d), zinc (7.12-9.92 mg/d), retinol (226.1-349.7 µg/d), riboflavin (0.44-0.70 mg/d) and docosahexaenoic acid (11.70-33.49 mg/d) amongst Sudanese women were very low compared with recommendations. CONCLUSION: The Sudanese diet was less diverse and differences in energy and nutrients intakes between groups were due to the amounts of food consumed. This view is supported by a lack of significant differences when intakes were expressed as proportion of whole energy bet

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Crawford MA, 2012, Pregnancy/Maternity and Child Development: The Challenge to Meet the Needs for the Brain and Sustainability of Homo Sapiens, ANNALS OF NUTRITION AND METABOLISM, Vol: 61, Pages: 323-323, ISSN: 0250-6807

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Crawford MA, Broadhurst CL, 2012, The role of docosahexaenoic and the marine food web as determinants of evolution and hominid brain development: the challenge for human sustainability., Nutr Health, Vol: 21, Pages: 17-39, ISSN: 0260-1060

Life originated on this planet about 3 billion years ago. For the first 2.5 billion years of life there was ample opportunity for DNA modification. Yet there is no evidence of significant change in life forms during that time. It was not until about 600 million years ago, when the oxygen tension rose to a point where air-breathing life forms became thermodynamically possible, that a major change can be abruptly seen in the fossil record. The sudden appearance of the 32 phyla in the Cambrian fossil record was also associated with the appearance of intracellular detail not seen in previous life forms. That detail was provided by cell membranes made with lipids (membrane fats) as structural essentials. Lipids thus played a major, as yet unrecognised, role as determinants in evolution. The compartmentalisation of intracellular, specialist functions as in the nucleus, mitochondria, reticulo-endothelial system and plasma membrane led to cellular specialisation and then speciation. Thus, not only oxygen but also the marine lipids were drivers in the Cambrian explosion. Docosahexaenoic acid (DHA) (all-cis-docosa-4,7,10,13,16,19-hexaenoic acid, C22:6ω3 or C22:6, n-3, DHA) is a major feature of marine lipids. It requires six oxygen atoms to insert its six double bonds, so it would not have been abundant before oxidative metabolism became plentiful. DHA provided the membrane backbone for the emergence of new photoreceptors that converted photons into electricity, laying the foundation for the evolution of other signalling systems, the nervous system and the brain. Hence, the ω3 DHA from the marine food web must have played a critical role in human evolution. There is also clear evidence from molecular biology that DHA is a determinant of neuronal migration, neurogenesis and the expression of several genes involved in brain growth and function. That same process was essential to the ultimate cerebral expansion in human evolution. There is now incontrovertible suppor

JOURNAL ARTICLE

Nyuar KB, Ghebremeskel K, Crawford MA, 2012, Sudanese women's and neonates' vitamin A status., Nutr Health, Vol: 21, Pages: 45-55, ISSN: 0260-1060

We have determined and compared the concentration levels of retinol and β-carotene in the plasma of three Sudanese women groups (displaced southern Sudanese women (DSSW), non-displaced southern Sudanese (NDSSW) and northern Sudanese women (NSW)), who were either pregnant or non-pregnant; and in their neonates (cord plasma). Plasma samples were analysed by high-performance liquid chromatography using reversed-phase column and diode-array detectors. The results revealed that retinol and β-carotene in the plasma of non-pregnant and pregnant women in the three groups were very low compared with studies reported elsewhere. Over 50% of pregnant DSSW and NDSSW had a low concentration of retinol plasma (< 0.70 µmol/L), and about 15-20% were deficient (< 0.35 µmol/L) according to World Health Organization criteria. Although the average retinol concentration in the plasma of pregnant NSW was > 0.70 µmol/L, which suggests sufficiency status, 32% showed lower levels and 10% were deficient. Plasma retinol β-carotene levels in the neonates' cords were also lower than their mothers and in comparison with other studies. These findings are in agreement with previous survey data and clinical reports, which also suggest that vitamin A deficiency is of great concern in the country. We concluded that insufficient intake of food of animal origin and repeated malarial and other parasitic diseases are the most likely causes of vitamin A deficiency.

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Broadhurst CL, Crawford M, Munro S, 2011, Littoral man and Waterside woman: The Crucial role of Marine and Lacustrine foods and Environmental Resources in the origin, Migration and Dominance of homo Sapiens, Was Man More Aquatic in the Past? Fifty Years After Alister Hardy - Waterside Hypotheses of Human Evolution, Pages: 16-35, ISBN: 9781608053551

The ability to exploit and thrive on a wide variety of foodstuffs from diverse environments is a hallmark of Homo sapiens. Humans are particularly well adapted to exploit waterside environments, where they can forage in areas offering protection from both terrestrial and aquatic predators. Humans are able to walk, run, climb, wade, swim and dive, and our research indicates that the most parsimonious explanation for this combination of locomotor traits, and for Man's current anatomy, physiology, nutritional requirements and unique intellect is evolution in a littoral environment. This model is consistent with the location and presumed palaeoecologies of all early Homo fossils and artifacts, and could help explain the rapid dispersal of Homo in the early Pleistocene (2.56-0.78 million years ago (Ma)), the colonization of Australia and Indonesia in the middle Pleistocene (0.78-0.13 Ma), and the rapid dispersal of Homo sapiens in the late Pleistocene (0.13-0.012 Ma). Reliance on the aquatic food chain is also a facile method for providing consistently abundant brain-specific nutrition for all members of a group or society, thus facilitating the development of the technology and culture that is uniquely human. © 2011 Bentham Science Publishers. All rights reserved.

BOOK CHAPTER

Daak AA, Ghebremeskel K, Elbashir MI, Bakhita A, Hassan Z, Crawford MAet al., 2011, Hydroxyurea therapy mobilises arachidonic Acid from inner cell membrane aminophospholipids in patients with homozygous sickle cell disease., J Lipids, Vol: 2011

The cytotoxic compound hydroxyurea (HU) is effective therapy for sickle cell disease. However, its effect on unsaturated membrane lipids is unknown. Red cell fatty acids were investigated in HU-treated (n = 19) and HU-untreated (n = 17) sickle cell patients and controls (n = 20). The HU-treated compared with the HU-untreated patients had lower arachidonic (AA) acid level in ethanolamine, physphoglycerids (EPG) (22.9 ± 1.2 versus 24.0 ± 1.1%, P < 0.05) serine SPG (22.13 ± 2.2 versus 24.9 ± 2.3%, P < 0.01) phosphoglycerides. The treated patients and controls had comparable levels of docosahexaenoic (DHA) and total n-3 fatty acids in EPG and choline phosphoglycerides (CPG). In contrast, the untreated group had significantly (P < 0.05) lower DHA and total n-3 compared with the controls in EPG (2.7 ± 0.4 versus 3.2 ± 0.6% and 4.6 ± 0.5 versus 5.2 ± 0.7%) and CPG (0.7 ± 0.2 versus 1.0 ± 0.2% and 1.2 ± 0.2 versus 1.4 ± 0.3). HU is known to activate cytosolic phospholipase A2 and cyclooxygenase 2, and from this study, it appears to induce mobilisation of AA from the inner cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may play a role in clinical improvements which occur in HU-treated patients.

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Kuipers RS, Luxwolda MF, Dijck-Brouwer DAJ, Eaton SB, Crawford MA, Cordain L, Muskiet FAJet al., 2010, Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet, BRITISH JOURNAL OF NUTRITION, Vol: 104, Pages: 1666-1687, ISSN: 0007-1145

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Brand A, Crawford MA, Yavin E, 2010, Retailoring docosahexaenoic acid-containing phospholipid species during impaired neurogenesis following omega-3 alpha-linolenic acid deprivation., J Neurochem, Vol: 114, Pages: 1393-1404

Diminished levels of docosahexaenoic acid (22:6n-3), the major fatty acid (FA) synthesized from alpha-linolenic acid (18:3n-3), have been implicated in functional impairment in the developing and adult brain. We have now examined the changes in phospholipid (PL) molecular species in the developing postnatal cortex, a region recently shown to be affected by a robust aberration in neuronal cell migration, after maternal diet alpha-linolenic acid deprivation (Yavin et al. (2009)Neuroscience162(4),1011). The frontal cortex PL composition of 1- to 4-week-old rats was analyzed by gas chromatography and electrospray ionization/tandem mass spectrometry. Changes in the cortical PL molecular species profile by dietary means appear very specific as 22:6n-3 was exclusively substituted by docosapentaenoic acid (22:5n-6). However, molecular species were conserved with respect to the combination of specific polar head groups (i.e. ethanolamine and serine) in sn-3 and defined saturated/mono-unsaturated FA in sn-1 position even when the sn-2 FA moiety underwent diet-induced changes. Our results suggest that substitution of docosahexaenoic acid by docosapentaenoic acid is tightly regulated presumably to maintain a proper biophysical characteristic of membrane PL molecular species. The importance of this conservation may underscore the possible biochemical consequences of this substitution in regulating certain functions in the developing brain.

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