bluuebunny/crossref_metadata_2025 huggingface dataset:
A ternary complex of hydroxycinnamoyl-CoA hydratase–lyase (HCHL) with acetyl-CoA and vanillin gives insights into substrate specificity and mechanism
Authors: Bennett Joseph P. , Bertin Lucille , Moulton Benjamin , Fairlamb Ian J. S. , Brzozowski A. Marek , Walton Nicholas J. , Grogan Gideon
Published: May 2008

HCHL (hydroxycinnamoyl-CoA hydratase–lyase) catalyses the biotransformation of feruloyl-CoA to acetyl-CoA and the important flavour–fragrance compound vanillin (4-hydroxy-3-methoxybenzaldehyde) and is exploited in whole-cell systems for the bioconversion of ferulic acid into natural equivalent vanillin. The reaction catalysed by HCHL has been thought to proceed by a two-step process involving first the hydration of the double bond of feruloyl-CoA and then the cleavage of the resultant β-hydroxy thioester by retro-aldol reaction to yield the products. Kinetic analysis of active-site residues identified using the crystal structure of HCHL revealed that while Glu-143 was essential for activity, Ser-123 played no major role in catalysis. However, mutation of Tyr-239 to Phe greatly increased the KM for the substrate ferulic acid, fulfilling its anticipated role as a factor in substrate binding. Structures of WT (wild-type) HCHL and of the S123A mutant, each of which had been co-crystallized with feruloyl-CoA, reveal a subtle helix movement upon ligand binding, the consequence of which is to bring the phenolic hydroxyl of Tyr-239 into close proximity to Tyr-75 from a neighbouring subunit in order to bind the phenolic hydroxyl of the product vanillin, for which electron density was observed. The active-site residues of ligand-bound HCHL display a remarkable three-dimensional overlap with those of a structurally unrelated enzyme, vanillyl alcohol oxidase, that also recognizes p-hydroxylated aromatic substrates related to vanillin. The data both explain the observed substrate specificity of HCHL for p-hydroxylated cinnamate derivatives and illustrate a remarkable convergence of the molecular determinants of ligand recognition between the two otherwise unrelated enzymes.
Spatial Extent and Figural Factors in Backward Masking
Authors: Geremek Adam , Spillmann Lothar
Published: May 2008

Spatial and figural characteristics of backward masking were studied, with two collinear arcs presented end-to-end and serving as target and mask, respectively. Stimulus onset asynchrony was 50 ms while interstimulus interval was 0 ms. Mask exposure duration required for masking was determined as a function of target length with mask length as a parameter. The exposure duration of the mask required for complete masking varied directly with target length, but inversely with mask length. The fact that masking strength increased with mask duration while all other parameters were kept constant suggests that masking depended on stimulus termination asynchrony. Maximal masking occurred for target arcs as long as 5.0 deg of visual angle, exceeding previously reported distances. Misaligned or differently shaped stimuli produced less masking, suggesting that figural factors play a role in long-range backward masking.
Was Helmholtz a Bayesian?
Authors: Westheimer Gerald
Published: May 2008

Modern developments in machine vision and object recognition have generated renewed interest in the proposal for drawing inferences put forward by the Rev. Thomas Bayes (1701–1759). In this connection the epistemological studies by Hermann Helmholtz (1821–1894) are often cited as laying the foundation of the currently popular move to regard perception as Bayesian inference. Helmholtz in his mature writings tried to reconcile the German idealist notions of reality-as-hypothesis with scientists' quests for the laws of nature, and espoused the view that we “attain knowledge of the lawful order in the realm of the real, but only in so far as it is represented in the tokens within the system of sensory impressions”. His propositions of inferring objects from internal sensory signals by what he called ‘unconscious inferences’ have made Helmholtz be regarded as a proto-Bayesian. But juxtaposing Bayes's original writings, the modern formulation of Bayesian inference, and Helmholtz's views of perception reveals only a tenuous relationship.
Can a low-gradient vertical-slot fishway provide passage for a lowland river fish community?
Authors: Stuart Ivor G. , Zampatti Brenton P. , Baumgartner Lee J.
Published: May 2008

Fishways are commonly used to restore native fish movements in regulated rivers. In the Murray-Darling Basin, Australia, 14 fishways are to be built by 2011 to improve passage along 2225 km of the river. The first of these fishways, constructed in 2003, is a vertical-slot design with low water velocities (0.98–1.4 m s–1) and turbulence (average 42 W m–3). This design was selected to provide passage for individuals between 20 and 1000 mm long. To determine passage success, trapping and a remote automated passive integrated transponder (PIT) tag reading system was used from October 2003 to February 2006. In 57 24-h samples at the exit (upstream end) and entrance (downstream end), 13 species and 30 409 fish were collected at a maximum rate of 4415 fish per day. Fish between 31 and 1030 mm successfully ascended the fishway. However, significantly smaller (<31 mm) fish and small-bodied (<50 mm) carp gudgeons (Hypseleotris spp.), a species previously considered non-migratory, were sampled downstream from the entrance of the fishway. The remote PIT tag reading system revealed that 81% of native golden perch (Macquaria ambigua) and 87% of non-native common carp (Cyprinus carpio) successfully ascended the fishway. These data will help maximise the efficiency of future fishways against a series of pre-determined performance criteria.
Superoxide dismutase 1 (SOD1) is essential for H
2
O
2
-mediated oxidation and inactivation of phosphatases in growth factor signaling
Authors: Juarez Jose C. , Manuia Mari , Burnett Mark E. , Betancourt Oscar , Boivin Benoit , Shaw David E. , Tonks Nicholas K. , Mazar Andrew P. , Doñate Fernando
Published: May 2008

Superoxide dismutase 1 (SOD1) is an abundant copper/zinc enzyme found in the cytoplasm that converts superoxide into hydrogen peroxide and molecular oxygen. Tetrathiomolybdate (ATN-224) has been recently identified as an inhibitor of SOD1 that attenuates FGF-2- and VEGF-mediated phosphorylation of ERK1/2 in endothelial cells. However, the mechanism for this inhibition was not elucidated. Growth factor (GF) signaling elicits an increase in reactive oxygen species (ROS), which inactivates protein tyrosine phosphatases (PTP) by oxidizing an essential cysteine residue in the active site. ATN-224-mediated inhibition of SOD1 in tumor and endothelial cells prevents the formation of sufficiently high levels of H
2
O
2
, resulting in the protection of PTPs from H
2
O
2
-mediated oxidation. This, in turn, leads to the inhibition of EGF-, IGF-1-, and FGF-2-mediated phosphorylation of ERK1/2. Pretreatment with exogenous H
2
O
2
or with the phosphatase inhibitor vanadate abrogates the inhibition of ERK1/2 phosphorylation induced by ATN-224 or SOD1 siRNA treatments. Furthermore, ATN-224-mediated SOD1 inhibition causes the down-regulation of the PDGF receptor. SOD1 inhibition also increases the steady-state levels of superoxide, which induces protein oxidation in A431 cells but, surprisingly, does not oxidize phosphatases. Thus, SOD1 inhibition in A431 tumor cells results in both prooxidant effects caused by the increase in the levels of superoxide and antioxidant effects caused by lowering the levels of H
2
O
2
. These results identify SOD1 as a master regulator of GF signaling and as a therapeutic target for the inhibition of angiogenesis and tumor growth.
Signal processing by the HOG MAP kinase pathway
Authors: Hersen Pascal , McClean Megan N. , Mahadevan L. , Ramanathan Sharad
Published: May 2008

Signaling pathways relay information about changes in the external environment so that cells can respond appropriately. How much information a pathway can carry depends on its bandwidth. We designed a microfluidic device to reliably change the environment of single cells over a range of frequencies. Using this device, we measured the bandwidth of the
Saccharomyces cerevisiae
signaling pathway that responds to high osmolarity. This prototypical pathway, the HOG pathway, is shown to act as a low-pass filter, integrating the signal when it changes rapidly and following it faithfully when it changes more slowly. We study the dependence of the pathway's bandwidth on its architecture. We measure previously unknown bounds on all of the
in vivo
reaction rates acting in this pathway. We find that the two-component Ssk1 branch of this pathway is capable of fast signal integration, whereas the kinase Ste11 branch is not. Our experimental techniques can be applied to other signaling pathways, allowing the measurement of their
in vivo
kinetics and the quantification of their information capacity.
Field-induced quantum critical route to a Fermi liquid in high-temperature superconductors
Authors: Shibauchi Takasada , Krusin-Elbaum Lia , Hasegawa Masashi , Kasahara Yuichi , Okazaki Ryuji , Matsuda Yuji
Published: May 2008

In high-transition-temperature (
T
c
) superconductivity, charge doping is a natural tuning parameter that takes copper oxides from the antiferromagnet to the superconducting region. In the metallic state above
T
c
, the standard Landau's Fermi-liquid theory of metals as typified by the temperature squared (
T
2
) dependence of resistivity appears to break down. Whether the origin of the non-Fermi-liquid behavior is related to physics specific to the cuprates is a fundamental question still under debate. We uncover a transformation from the non-Fermi-liquid state to a standard Fermi-liquid state driven not by doping but by magnetic field in the overdoped high-
T
c
superconductor Tl
2
Ba
2
CuO

6+
x

. From the
c
-axis resistivity measured up to 45 T, we show that the Fermi-liquid features appear above a sufficiently high field that decreases linearly with temperature and lands at a quantum critical point near the superconductivity's upper critical field—with the Fermi-liquid coefficient of the
T
2
dependence showing a power-law diverging behavior on the approach to the critical point. This field-induced quantum criticality bears a striking resemblance to that in quasi-two-dimensional heavy-Fermion superconductors, suggesting a common underlying spin-related physics in these superconductors with strong electron correlations.
A gastrolith protein serving a dual role in the formation of an amorphous mineral containing extracellular matrix
Authors: Shechter Assaf , Glazer Lilah , Cheled Shira , Mor Eyal , Weil Simy , Berman Amir , Bentov Shmuel , Aflalo Eliahu D. , Khalaila Isam , Sagi Amir
Published: May 2008

Despite the proclamation of Lowenstam and Weiner that crustaceans are the “champions of mineral mobilization and deposition of the animal kingdom,” relatively few proteins from the two main calcification sites in these animals, i.e., the exoskeleton and the transient calcium storage organs, have been identified, sequenced, and their roles elucidated. Here, a 65-kDa protein (GAP 65) from the gastrolith of the crayfish,
Cherax quadricarinatus
, is fully characterized and its function in the mineralization of amorphous calcium carbonate (ACC) of the extracellular matrix is demonstrated. GAP 65 is a negatively charged glycoprotein that possesses three predicted domains: a chitin-binding domain 2, a low-density lipoprotein receptor class A domain, and a polysaccharide deacetylase domain. Expression of
GAP 65
was localized to columnar epithelial cells of the gastrolith disk during premolt.
In vivo
administration of
GAP 65
dsRNA resulted in a significant reduction of
GAP 65
transcript levels in the gastrolith disk. Such gene silencing also caused dramatic structural and morphological deformities in the chitinous-ACC extracellular matrix structure. ACC deposited in these gastroliths appeared to be sparsely packed with large elongated cavities compared with the normal gastrolith, where ACC is densely compacted. ACC spherules deposited in these gastroliths are significantly larger than normal. GAP 65, moreover, inhibited calcium carbonate crystallization
in vitro
and stabilized synthetic ACC. Thus, GAP 65 is the first protein shown to have dual function, involved both in extracellular matrix formation and in mineral deposition during biomineralization.
Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and Aβ accumulation
Authors: Muhammad Alim , Flores Ingrid , Zhang Hong , Yu Rui , Staniszewski Agnieszka , Planel Emmanuel , Herman Mathieu , Ho Lingling , Kreber Robert , Honig Lawrence S. , Ganetzky Barry , Duff Karen , Arancio Ottavio , Small Scott A.
Published: May 2008

Although deficiencies in the retromer sorting pathway have been linked to late-onset Alzheimer's disease, whether these deficiencies underlie the disease remains unknown. Here we characterized two genetically modified animal models to test separate but related questions about the effects that retromer deficiency has on the brain. First, testing for cognitive defects, we investigated retromer-deficient mice and found that they develop hippocampal-dependent memory and synaptic dysfunction, which was associated with elevations in endogenous Aβ peptide. Second, testing for neurodegeneration and amyloid deposits, we investigated retromer-deficient flies expressing human wild-type amyloid precursor protein (APP) and human β-site APP-cleaving enzyme (BACE) and found that they develop neuronal loss and human Aβ aggregates. By recapitulating features of the disease, these animal models suggest that retromer deficiency observed in late-onset Alzheimer's disease can contribute to disease pathogenesis.
Chaperone-dependent amyloid assembly protects cells from prion toxicity
Authors: Douglas Peter M. , Treusch Sebastian , Ren Hong-Yu , Halfmann Randal , Duennwald Martin L. , Lindquist Susan , Cyr Douglas M.
Published: May 2008

Protein conformational diseases are associated with the aberrant accumulation of amyloid protein aggregates, but whether amyloid formation is cytotoxic or protective is unclear. To address this issue, we investigated a normally benign amyloid formed by the yeast prion [
RNQ
+
]. Surprisingly, modest overexpression of Rnq1 protein was deadly, but only when preexisting Rnq1 was in the [
RNQ
+
] prion conformation. Molecular chaperones protect against protein aggregation diseases and are generally believed to do so by solubilizing their substrates. The Hsp40 chaperone, Sis1, suppressed Rnq1 proteotoxicity, but instead of blocking Rnq1 protein aggregation, it stimulated conversion of soluble Rnq1 to [
RNQ
+
] amyloid. Furthermore, interference with Sis1-mediated [
RNQ
+
] amyloid formation exacerbated Rnq1 toxicity. These and other data establish that even subtle changes in the folding homeostasis of an amyloidogenic protein can create a severe proteotoxic gain-of-function phenotype and that chaperone-mediated amyloid assembly can be cytoprotective. The possible relevance of these findings to other phenomena, including prion-driven neurodegenerative diseases and heterokaryon incompatibility in fungi, is discussed.
Estradiol modulation of phenylephrine-induced excitatory responses in ventromedial hypothalamic neurons of female rats
Authors: Lee Anna W. , Kyrozis Andreas , Chevaleyre Vivien , Kow Lee-Ming , Devidze Nino , Zhang Qiuyu , Etgen Anne M. , Pfaff Donald W.
Published: May 2008

Estrogens act within the ventromedial nucleus of the hypothalamus (VMN) to facilitate lordosis behavior. Estradiol treatmentin vivoinduces α1b-adrenoreceptor mRNA and increases the density of α1B-adrenoreceptor binding in the hypothalamus. Activation of hypothalamic α1-adrenoceptors also facilitates estrogen-dependent lordosis. To investigate the cellular mechanisms of adrenergic effects on VMN neurons, whole-cell patch-clamp recordings were carried out on hypothalamic slices from control and estradiol-treated female rats. In control slices, bath application of the α1-agonist phenylephrine (PHE; 10 μM) depolarized 10 of 25 neurons (40%), hyperpolarized three neurons (12%), and had no effect on 12 neurons (48%). The depolarization was associated with decreased membrane conductance, and this current had a reversal potential close to the K+equilibrium potential. The α1b-receptor antagonist chloroethylclonidine (10 μM) blocked the depolarization produced by PHE in all cells. From estradiol-treated rats, significantly more neurons in slices depolarized (71%) and fewer neurons showed no response (17%) to PHE. PHE-induced depolarizations were significantly attenuated with 4-aminopyridine (5 mM) but unaffected by tetraethylammonium chloride (20 mM) or blockers of Na+and Ca2+channels. These data indicate that α1-adrenoceptors depolarize VMN neurons by reducing membrane conductance for K+. Estradiol amplifies α1b-adrenergic signaling by increasing the proportion of VMN neurons that respond to stimulation of α1b-adrenergic receptors, which is expected in turn to promote lordosis.
Effect of cold exposure on energy balance and liver respiratory capacity in post-weaning rats fed a high-fat diet
Authors: Iossa Susanna , Lionetti Lillà , Mollica Maria P. , Crescenzo Raffaella , Barletta Antonio , Liverini Giovanna
Published: May 2008

Variations in energy balance, body composition, and nutrient partitioning induced by high-fat feeding, cold exposure or by concomitant high-fat feeding and cold exposure were studied in young Wistar rats. Changes in hepatic metabolism as well as in serum free triiodothyronine and leptin levels were also evaluated. Rats were exposed to either 24 or 4°C and fed either a low- or high-fat diet (10 % or 50 % energy respectively) for 2 weeks. Relative to low-fat feeding at 24°C, both energy intake and expenditure were increased by high-fat feeding or by cold exposure, and these changes were accompanied by increased serum triiodothyronine levels. In response to concomitant high-fat feeding and cold exposure, serum triiodothyronine tended to be further elevated, but no further increases in energy intake or energy expenditure were observed. Independently of diet, the increased energy expenditure in cold-exposed rats was not completely balanced by adaptive hyperphagia, with consequential reductions in protein and fat gain, accompanied by marked decreases in serum leptin. Furthermore, unlike high-fat feeding at 24°C, cold exposure enhanced hepatic mitochondrial oxidative capacity both in the low-fat- and high-fat-fed groups. It is concluded that in this strain of young Wistar rats, despite similarly marked stimulation of energy expenditure by high-fat feeding at 24°C, by cold exposure and by concomitant high-fat feeding and cold exposure, an increased hepatic oxidative capacity occurred only in the presence of the cold stimulus.
Manipulating the fatty acid composition of muscle and adipose tissue in beef cattle
Authors: Scollan Nigel D. , Choi Nag-Jin , Kurt Esra , Fisher Alan V. , Enser Mike , Wood Jeff D.
Published: May 2008

Enhancing then-3 polyunsaturated fatty acid (PUFA) content of beef is important in view of the generally saturated nature of fatty acids in ruminant meats and the negative effect this can have on human health. This study examined the effects of different sources of dietaryn-3 PUFA on the performance of steers and the fatty acid composition ofm. longissimus thoracismuscle and associated subcutaneous adipose tissue. Animals were fedad libitumon grass silage plus one of four concentrates (60:40 forage:concentrate on a DM basis) containing differing sources of lipid: Megalac (16:0), lightly bruised whole linseed (18:3n-3), fish oil (20:5n-3 and 22:6n-3) and a mixture of linseed and fish oil (1:1, on an oil basis). Diets were formulated so that total dietary oil intake was 6 %, approximately half of which was from the experimental test oil. Linseed feeding not only increased the levels of 18:3n-3 in muscle phospholipid from 9·5 to 19 mg/100 g muscle but also enhanced the synthesis of 20:5n-3, the level of which increased from 10 to 15 mg/100 g muscle. Linseed also increased the proportion of 18:3n-3 in muscle neutral lipid and in adipose tissue lipids by a factor of 1·64 and 1·75 respectively. Fish oil feeding doubled the proportion of 20:5n-3 and 22:6n-3 in muscle phospholipids. The proportion of 18:1transin muscle neutral lipid was higher on then-3 PUFA diets than the control diet, 0·04 and 0·02 respectively. Despite the implied modification to rumen metabolism, lipid source did not affect feed intake, growth rate, cold carcass weight or carcass fatness, but carcass conformation score was higher on fish oil treatments (P<0·05). However, total muscle fatty acid content was not different between treatments and ranged from 3·5–4·3 % of tissue weight. The increase inn-3 PUFA in the meat produced by feeding linseed or fish oil lowered then-6:n-3 ratio but had little effect on the P:S ratio.
Combined effects of red pepper and caffeine consumption on 24 h energy balance in subjects given free access to foods
Authors: Yoshioka Mayumi , Doucet Eric , Drapeau Vicky , Dionne Isabelle , Tremblay Angelo
Published: May 2008

The effects of red pepper and caffeine ingestion on energy and macronutrient balances were examined in eight Caucasian male subjects. All subjects participated in two randomly assigned conditions: control and experimental (red pepper and caffeine). After ingesting a standardized breakfast, subjects ate three mealsad libitum(lunch, dinner and breakfast) and snacks which were served approximately 2 h after the lunch and dinner over a 24 h period. Two appetizers (2×322 kJ with or without 3 g red pepper) were given before lunch and dinner, and a drink (decaffeinated coffee with or without 200 mg caffeine) was served at all meals and snacks except for the after-dinner snack. It is also important to note that on the experimental day, 8.6 and 7.2 g red pepper were also added to lunch and dinner respectively. Red pepper and caffeine consumption significantly reduced the cumulativead libitumenergy intake and increased energy expenditure. The mean difference in energy balance between both conditions was 4000 kJ/d. Moreover, the power spectral analysis of heart rate suggested that this effect of red pepper was associated with an increase in sympathetic:parasympathetic nervous system activity ratio. These results indicate that the consumption of red pepper and caffeine can induce a considerable change in energy balance when individuals are given free access to foods.
Second meal effect: modified sham feeding does not provoke the release of stored triacylglycerol from a previous high-fat meal
Authors: Jackson Kim G. , Denise Robertson M. , Fielding Barbara A. , Frayn Keith N. , Williams Christine M.
Published: May 2008

The present study was carried out to determine whether cephalic stimulation, associated with eating a meal, was sufficient stimulus to provoke the release of stored triacylglycerol (TAG) from a previous high-fat meal. Ten subjects were studied on three separate occasions. Following a 12 h overnight fast, subjects were given a standard mixed test meal which contained 56 g fat. Blood samples were taken before the meal and for 5 h after the meal when the subjects were randomly allocated to receive either water (control) or were modified sham fed a low-fat (6 g fat) or moderate-fat (38 g fat) meal. Blood samples were collected for a further 3 h. Compared with the control, modified sham feeding a low- or moderate-fat meal did not provoke an early entry of TAG, analysed in either plasma or TAG-rich lipoprotein (TRL) fraction (density <1.006 kg/l). The TRL-retinyl ester data showed similar findings. A cephalic phase secretion of pancreatic polypeptide, without a significant increase in cholecystokinin levels, was observed on modified sham feeding. Although these data indicate that modified sham feeding was carried out successfully, analysis of the fat content of the expectorant showed that our subjects may have accidentally ingested a small amount of fat (0.7 g for the low-fat meal and 2.4 g for the moderate-fat meal). Nevertheless, an early TAG peak following modified sham feeding was not demonstrated in the present study, suggesting that significant ingestion of food, and not just oro-sensory stimulation, is necessary to provoke the release of any TAG stored from a previous meal.
Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders
Authors: Darlington L. Gail , Stone Trevor W.
Published: May 2008

The generation of reactive oxygen species (free radicals) is an important factor in the development and maintenance of rheumatoid arthritis in humans and animal models. One source of free radicals is nitric oxide produced within the synoviocytes and chondrocytes and giving rise to the highly toxic radical peroxynitrite. Several cytokines, including tumour necrosis factor-α (TNFα) are involved in the formation of free radicals, partly by increasing the activity of nitric oxide synthase. Indeed, nitric oxide may mediate some of the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines, steroids and methotrexate can suppress nitric oxide synthase. Dietary antioxidants include ascorbate and the tocopherols and beneficial effects of high doses have been reported especially in osteoarthritis. There is also evidence for beneficial effects of β-carotene and selenium, the latter being a component of the antioxidant enzyme glutathione peroxidase. The polyunsaturated fatty acids (PUFA) include then-3 compounds, some of which are precursors of eicosanoid synthesis, and then-6 group which can increase formation of the pro-inflammatory cytokines TNFα and interleukin-6, and of reactive oxygen species. Some prostaglandins, however, suppress cytokine formation, so thatn-3 PUFA often oppose the inflammatory effects of somen-6-PUFA. γ-linolenic acid (GLA) is a precursor of prostaglandin E1, a fact which may account for its reported ability to ameliorate arthritic symptoms. Fish oil supplements, rich inn-3 PUFA such as eicosapentaenoic acid have been claimed as beneficial in rheumatoid arthritis, possibly by suppression of the immune system and its cytokine repertoire. Some other oils of marine origin (e.g. from the green-lipped mussel) and a range of vegetable oils (e.g. olive oil and evening primrose oil) have indirect anti-inflammatory actions, probably mediated via prostaglandin E1. Overall, there is a growing scientific rationale for the use of dietary supplements as adjuncts in the treatment of inflammatory disorders such as rheumatoid arthritis and osteoarthritis.
Dietary patterns and mortality in Danish men and women: a prospective observational study
Authors: Osler Merete , Heitmann Berit L. , Gerdes Lars U. , Jørgensen Lillian M. , Schroll Marianne
Published: May 2008

The analysis of dietary patterns emerged recently as a possible approach to examining diet–disease relation. We analysed the risk of all-cause and cardiovascular mortality associated with dietary patterns in men and women, while taking a number of potential confounding variables into account. Data were from a prospective cohort study with follow-up of total and cause-specific mortality. A random sample of 3698 men and 3618 women aged 30–70 years and living in Copenhagen County, Denmark, were followed from 1982 to 1998 (median 15 years). Three dietary patterns were identified from a twenty-eight item food frequency questionnaire, collected at baseline: (1) a predefined healthy food index, which reflected daily intakes of fruits, vegetables and wholemeal bread, (2) a prudent and (3) a Western dietary pattern derived by principal component analysis. The prudent pattern was positively associated with frequent intake of wholemeal bread, fruits and vegetables, whereas the Western was characterized by frequent intakes of meat products, potatoes, white bread, butter and lard. Among participants with complete information on all variables, 398 men and 231 women died during follow-up. The healthy food index was associated with reduced all-cause mortality in both men and women, but the relations were attenuated after adjustment for smoking, physical activity, educational level, BMI, and alcohol intake. The prudent pattern was inversely associated with all-cause and cardiovascular mortality after controlling for confounding variables. The Western pattern was not significantly associated with mortality. This study partly supports the assumption that overall dietary patterns can predict mortality, and that the dietary pattern associated with the lowest risk is the one which is in accordance with the current recommendations for a prudent diet.
An olive oil-rich diet reduces scavenger receptor mRNA in murine macrophages
Authors: Miles Elizabeth A. , Wallace Fiona A. , Calder Philip C.
Published: May 2008

During atherogenesis, a pathological accumulation of lipids occurs within aortic intimal macrophages through uptake of oxidised LDL via scavenger receptors. Here we investigated whether some of the anti-atherosclerotic effects ascribed to an olive oil rich-diet are mediated through effects on macrophage scavenger receptors (MSR). Male C57 Bl6 mice aged 6 weeks were fed for 12 weeks on a low-fat diet (containing 25 g corn oil/kg) or on high-fat diets containing 200 g coconut oil, olive oil or safflower oil/kg. Thioglycollate-elicited peritoneal macrophages were analysed for fatty acid composition by GC and the levels of mRNA coding for three MSR (MSRA type I, MSRA type II and CD36) were measured by reverse-transcription polymerase chain reaction. Feeding mice diets enriched with different fats resulted in significant differences in the fatty acid profile of macrophages, which reflected the fatty acid compositions of the diets. These differences were accompanied by a lower level of mRNA for MSRA type I, MSRA type II and CD36 in macrophages from mice fed an olive-oil-enriched diet compared with the mice fed on the low-fat diet. These data suggest that part of the protective effect of olive oil against atherosclerosis might be via reducing macrophage uptake of oxidised LDL. Whether this effect is due to the downregulation of gene transcription directly by unsaturated fatty acids or is the result of the effect of monounsaturated fatty acids or other components of olive oil on LDL composition and oxidation remains to be ascertained.
The hypocholesterolaemic effects of sitostanol in the guinea pig are in part related to changes in hepatic lipids and lipoprotein composition
Authors: Ramjiganesh Tripurasundari , Roy Suheeta , McIntyre Jonathan C. , Luz Fernandez Maria
Published: May 2008

To evaluate some of the mechanisms involved in the plasma cholesterol lowering of sitostanol (SI), male Hartley guinea pigs were fed diets containing cholesterol (0.25 g/100 g) and four doses of SI: either 0 (control), 0.75, 1.5 or 2.25 g/100 g. In addition a negative control (-C) group with dietary cholesterol (0.04 g/100 g) was included. Corn oil was used as the source of fat and the contribution of fat energy was 35 %. Plasma total cholesterol was 43, 49 and 53 % (P<0.0001) lower after SI intake compared to the control. Plasma LDL concentrations were 47, 53 and 61 % lower with increasing doses of SI. In addition, intake of SI resulted in 26–42 % lower hepatic total cholesterol. Hepatic esterified cholesterol and triacylglycerols were 32–60 % and 55–61 % lower after SI intake. SI intake resulted in favourable plasma and hepatic cholesterol concentrations similar to those in guinea pigs fed low levels of dietary cholesterol (-C). The LDL obtained from the control group had a higher number of molecules of free and esterified cholesterol than the SI groups. SI intake resulted in 69–71 % higher cholesterol excretion compared to the control. SI treatment enhanced the total faecal neutral sterol excretion by 54–58 % compared to control and by 70–76 % compared to the (-C) group. These results suggest that SI might have its hypocholesterolaemic effect by reducing cholesterol absorption, which results in lower concentration of cholesterol in liver. This reduction in hepatic cholesterol might possibly alter hepatic cholesterol metabolism and affect lipoprotein concentration and composition.
Effects of maternal iron restriction in the rat on hypoxia-induced gene expression and fetal metabolite levels
Authors: Lewis Rohan M. , James Lynwen A. , Zhang Junlong , Byrne Christopher D. , Nicholas Hales C.
Published: May 2008

The mechanism by which maternal Fe deficiency in the rat causes fetal growth retardation has not been clearly established. This study compared the effects on the fetuses from dams fed a control diet with two groups of dams fed Fe-restricted diets. One Fe-restricted group was fed the Fe-restricted diet for 1 week prior to mating and throughout gestation and the second Fe-restricted group was fed the Fe-restricted diet for 2 weeks prior to mating and throughout gestation. On day 21 of gestation Fe-restricted dams, and their fetuses, were anaemic. Fetal weight was reduced in both Fe-restricted groups compared with controls. Expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) are induced by hypoxia. The levels of HIF-1α mRNA were highest in placenta, then in kidney, heart and liver but were not different between the groups. Levels of plasma VEGF were not different between the groups. Maternal plasma triacylglycerol was decreased in the 1-week Fe-restricted dams compared with controls. Maternal plasma cholesterol and free fatty acid levels were not different between the groups. In fetal plasma, levels of triacylglycerol and cholesterol were decreased in both Fe-restricted groups. In maternal plasma, levels of a number of amino acids were elevated in both Fe-restricted groups. In contrast, levels of a number of amino acids in fetal plasma were lower in both Fe-restricted groups. Fetal plasma lactate was increased in Fe-restricted fetuses but fetal plasma glucose and β-hydroxybutyrate were not affected. These changes in fetal metabolism may contribute to fetal growth retardation in this model. This study does not support the hypothesis that the Fe-restricted fetus is hypoxic.
Dose-dependent bone-sparing effects of dietary isoflavones in the ovariectomised rat
Authors: Picherit Christel , Chanteranne Brigitte , Bennetau-Pelissero Catherine , Davicco Marie-Jeanne , Lebecque Patrice , Barlet Jean-Pierre , Coxam Véronique
Published: May 2008

The dose-dependent bone-sparing effects of dietary isoflavones (IF) were investigated in adult (7-month-old) Wistar rats. Forty animals were ovariectomised, allocated into four groups of ten rats each, and immediately treated orally with IF at 0 (OVX), 20 (IF20), 40 (IF40) or 80 (IF80) μg/g body weight per d for 91 d; ten sham-operated (SH) controls received the same diet without added IF. Animals were killed on day 91. Both femoral failure load and total femoral, diaphyseal or metaphyseal bone mineral densities (BMD) were lower in OVX animals than in SH animals. Urinary deoxypyridinoline (DPD) excretion, a marker of bone resorption, and plasma osteocalcin (OC) levels, a marker of osteoblast activity, were higher in OVX animals than in SH animals. Total femoral and diaphyseal BMD and femoral failure load were similar in IF-treated rats and SH rats. Although metaphyseal BMD in IF40 or IF80 rats was similar to that in SH rats, its value was lower in IF20 rats than in controls. The day 91 urinary DPD excretion in IF40 and IF80 rats, but not in IF20 rats, was similar to that in SH rats. Day 91 plasma OC concentrations in IF-treated rats were similar to day 45 values, but were decreased in OVX and SH rats. Thus, daily IF consumption prevented ovariectomy-induced bone loss, both by depressing bone resorption and stimulating osteoblast activity. Moreover, as only the highest IF level induced a weak uterotrophic activity, the optimal IF dose which preserves both cancellous and cortical bone, but exhibits no oestrogen-like effects on the uterus, was 40 μg/g body weight per d.
Dietary patterns and their association with food and nutrient intake in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam study
Authors: Schulze Matthias B. , Hoffmann Kurt , Kroke Anja , Boeing Heiner
Published: May 2008

Dietary pattern analysis has recently received growing attention, as it might be more appropriate in studies of diet–disease associations than the single food or nutrient approach that has dominated past epidemiological research. Factor analysis is a technique which is commonly used to identify dietary patterns within study populations. However, the ability of factor solutions to account for variance of food and nutrient intake has so far remained unclear. The present study therefore explored the statistical properties of dietary patterns with regard to the explained variance. Food intake of 8975 men and 13 379 women, assessed by a food-frequency questionnaire, was aggregated into forty-seven separate food groups. Dietary patterns were identified by principal component analysis and subsequent varimax rotation. Seven factors were retained for both men and women, which accounted for about 31 % of the total variance. The explained variance was relatively high (>40 %) for cooked vegetables, sauce, meat, dessert, cake, bread other than wholemeal, raw vegetables, processed meat, high-fat cheese, butter and margarine. Factor scores were used to investigate associations between the factors and nutrient intake. The patterns accounted for relatively large proportions of variance of energy and macronutrient intake, but for less variance of alcohol and micronutrient intake, especially of retinol, β-carotene, vitamin E, Ca and ascorbic acid. In addition, factors were related to age, BMI, physical activity, education, smoking and vitamin and mineral supplement use.
Tolerance to low-digestible carbohydrates: symptomatology and methods
Authors: Marteau Philippe , Flourié Bernard
Published: May 2008

Low-digestible carbohydrates (LDCs) are incompletely or not absorbed in the small bowel and fermented in the colon. They are usually well tolerated but may also have some dose-related undesirable effects due to their natural osmotic potential and/or excessive fermentation: borborygmi, excessive flatus, bloating, abdominal cramps and eventually diarrhoea. There is an important intersubject variability in the tolerance to LDCs because of differences in absorption capacity, motility pattern, colonic response and intestinal sensitivity. There is also a great intrasubject variability, depending on the type of LDC, dosage and type of consumption. Absorption of LDC in the small intestine can be assessed using hydrogen breath test or intubation techniques or analysis of ileostomy effluents. Double-blind, placebo-controlled studies are required to assess the subjective symptoms of intolerance, and the experimental conditions may influence the results.
Beneficial health effects of low-digestible carbohydrate consumption
Authors: Scheppach Wolfgang , Luehrs Hardi , Menzel Thomas
Published: May 2008

Low-digestible carbohydrates represent a class of enzyme-resistant saccharides that have specific effects on the human gastrointestinal tract. In the small bowel, they affect nutrient digestion and absorption, glucose and lipid metabolism and protect against known risk factors of cardiovascular disease. In the colon they are mainly degraded by anaerobic bacteria in a process called fermentation. As a consequence, faecal nitrogen excretion is enhanced, which is used clinically to prevent or treat hepatic encephalopathy. Low-digestible carbohydrates are trophic to the epithelia of the ileum and colon, which helps to avoid bacterial translocation. Short-chain fatty acids are important fermentation products and are evaluated as new therapeutics in acute colitis. They are considered in the primary prevention of colorectal cancer. The bifidogenic effect of fructo-oligosaccharides merits further attention. Unfermented carbohydrates increase faecal bulk and play a role in the treatment of chronic functional constipation, symptomatic diverticulosis and, possibly, the irritable bowel syndrome. In conclusion, low-digestible carbohydrates may play a role in the maintenance of human digestive health. However, the strength of evidence differs between disease entities.
Non-polyol low-digestible carbohydrates: food applications and functional benefits
Authors: Murphy Olive
Published: May 2008

Many LDCs currently on the market are not digested in the upper gastrointestinal tract and become fermented in the large intestine. They possess physiological benefits similar to those of dietary fibre. For some of these materials the fermentation process is highly specialised and leads to the selective stimulation and growth of beneficial gut bacteria, e.g. bifidobacteria. These materials are described as prebiotics, which are defined as nutrients fermented in the large bowel that favour the growth of desirable large bowel microflora. This activity has been demonstrated for inulin and oligofructose. Two other carbohydrates with low digestibility that offer desirable physiological properties are resistant starch (RS) and polydextrose (PD). These ‘functional’ benefits have led to considerable interest from the food industry leading to the use of these ingredients in the development of new ‘healthy’ products. This paper describes the use of these materials in the development of ‘healthy’ products, some of their functional properties, and the benefits they confer on different food systems.
Effects of an exogenous enzyme preparation on microbial protein synthesis, enzyme activity and attachment to feed in the Rumen Simulation Technique (Rusitec)
Authors: Wang Y. , McAllister T. A. , Rode L. M. , Beauchemin K. A. , Morgavi D. P. , Nsereko V. L. , Iwaasa A. D. , Yang W.
Published: May 2008

The effects of an exogenous enzyme preparation, the application method and feed type on ruminal fermentation and microbial protein synthesis were investigated using the rumen simulation technique (Rusitec). Steam-rolled barley grain and chopped alfalfa hay were sprayed with water (control, C), an enzyme preparation with a predominant xylanase activity (EF), or autoclaved enzyme (AEF) 24 h prior to feeding, or the enzyme was supplied in the buffer infused into the Rusitec (EI). Microbial N incorporation was measured using (15NH4)2SO4in the buffer. Spent feed bags were pummelled mechanically in buffer to segregate the feed particle-associated (FPA) and feed particle-bound (FPB) bacterial fractions. Enzymes applied to feed reduced neutral-detergent fibre content, and increased the concentration of reducing sugars in barley grain, but not alfalfa hay. Ruminal cellulolytic bacteria were more numerous with EF than with C. Disappearance of DM from barley grain was higher with EF than with C, but alfalfa was unaffected by EF. Treatment EF increased incorporation of15N into FPA and FPB fractions at 24 and 48 h. In contrast, AEF reduced the 24 h values, relative to C; AEF and C were similar at 48 h. Infused enzyme (EI) did not affect15N incorporation. Xylanase activity in effluent was increased by EF and EI, compared to C, but not by AEF. Xylanase activity in FPA was higher at 48 h than at 24 h with all treatments; it was higher with EF than C at 24 and 48 h, but was not altered by AEF or EI. Applying enzymes onto feeds before feeding was more effective than dosing directly into the artificial rumen for increasing ruminal fibrolytic activity.
Dietary fat intake in healthy adolescents: inverse relationships between the estimated intake of saturated fatty acids and serum cholesterol
Authors: Samuelson Gösta , Bratteby Lars-Erik , Mohsen Rawya , Vessby Bengt
Published: May 2008

The objective of the present study was to describe the intake of dietary fatty acids among healthy 15-year-old boys and girls and to relate the intake of specific fatty acids and the fatty acid composition of the serum cholesterol esters to serum lipid, apolipoprotein (Apo) and insulin concentrations respectively. Fifty-two girls and forty-two boys were randomly selected from the official population register. Unexpectedly, significant inverse associations were found between the dietary content of saturated fatty acids with a chain length of four to fifteen C atoms, mainly derived from milk fat, as well as the corresponding fatty acids in the serum cholesterol esters, on the one hand and the serum concentrations of cholesterol and ApoB on the other. The estimated dietary intake of 4:0–10:0, 12:0 and 14:0 respectively, were all significantly inversely related to the serum cholesterol (r-0.32,r-0.31,r-0.30, all P<0.05) and ApoB (r-0.42,r-0.42, andr-0.40, all P<0.05) concentrations in girls and 12:0 to the ApoB concentration (r-0.55, P<0.01) in boys. The proportions of 12:0 and 15:0 in the serum cholesterol esters were negatively correlated with the serum cholesterol concentrations in both girls (r-0.34,r-0.32, P<0.05) and boys (r-0.53, P<0.01;r-0.32, P<0.05) and with the ApoB concentrations among boys (r-0.61, P<0.01;r-0.43, P<0.05). It is conceivable that milk fat contains or is associated with some component in the diet, or some other characteristics of the food intake, which counterbalances the expected positive relationships between saturated fat intake and lipid levels.
Selenium in global food systems
Authors: Combs Gerald F.
Published: May 2008

Food systems need to produce enough of the essential trace element Se to provide regular adult intakes of at least 40 μg/d to support the maximal expression of the Se enzymes, and perhaps as much as 300 μg/d to reduce risks of cancer. Deprivation of Se is associated with impairments in antioxidant protection, redox regulation and energy production as consequences of suboptimal expression of one or more of the Se-containing enzymes. These impairments may not cause deficiency signs in the classical sense, but instead contribute to health problems caused by physiological and environmental oxidative stresses and infections. At the same time, supranutritional intakes of Se, i.e. intakes greater than those required for selenocysteine enzyme expression, appear to reduce cancer risk. The lower, nutritional, level is greater than the typical intakes of many people in several parts of the world, and few populations have intakes approaching the latter, supranutritional, level. Accordingly, low Se status is likely to contribute to morbidity and mortality due to infectious as well as chronic diseases, and increasing Se intakes in all parts of the world can be expected to reduce cancer rates.